News prior to 2019 archived

Meet the Researcher: Danny Veronese-Paniagua

By Erika Brown – October 1, 2024

Daniel Veronese-Paniagua, a sixth-year graduate student in the Millman Lab, recently published his first first-authorship as a preprint in bioRxiv. The study, titled Coxsackievirus B infection invokes unique cell-type specific responses in primary human pancreatic islets, sheds new light on the intricate mechanisms through which Coxsackievirus B3 (CVB) may trigger type 1 diabetes (T1D). The study was conducted by Veronese-Paniagua, Dr. Jeffrey Millman, Dr. Hubert Tse of the University of Kansas Medical Center, and their colleagues at Washington University School of Medicine and the University of Kansas Medical Center. It utilized single-cell RNA sequencing to uncover distinct responses within pancreatic islet cell types—specifically β, α, and ductal cells—following CVB infection.

CVB has long been suspected to play a role in the onset of T1D, an autoimmune condition in which the immune system attacks insulin-producing β cells in the pancreas. Veronese-Paniagua’s study provides crucial insights into how this virus induces transcriptional changes that disrupt cellular functions vital for maintaining glucose homeostasis. This preprint publication marks a significant milestone in advancing the understanding of the link between viral infections and the development of T1D, offering new avenues for clinical research and treatment development. It underscores the complex interplay between viral infections, cellular responses, and autoimmune diseases like T1D. As research continues to unravel these connections, there is hope for future treatments that could preserve pancreatic function and improve outcomes for individuals at risk of developing diabetes.

Veronese-Paniagua grew up in an underserved community and attended a high school with a limited science department. “When I started college, I knew I liked science, but my only concepts of science were engineering, medicine, and teaching. I knew I didn’t want to teach, I knew I didn’t want to be an engineer, so I said to myself, ‘Okay, my next thing is to go into medicine.’ Thankfully, within my first year of college, I discovered the world of research, and I fell in love with it.” He finds it “addicting” to discover new things in research. “[It’s addicting] to have a question and to find an answer that may fit your expectations, but it has more to it, it’s more complex than you thought it was. You expect the complexity, but sometimes the level of complexity is beyond your imagination.”

After earning his Bachelor of Arts in Biology from Cornell, he worked as a research technician at Washington University for two years, studying colorectal cancer in the Blair Madison Lab. This experience sparked his interest in stem cell biology. While Veronese-Paniagua initially wanted to move on from Washington University after his time in the Madison Lab, he later realized and appreciated the school’s strong student support and diversity, which made him feel more comfortable than other places he interviewed at. Veronese-Paniagua joined the Millman Lab in 2020 as a student in the Developmental, Regenerative, and Stem Cell Biology Program. He was attracted to the lab’s working dynamic as well as the translational research. “You can see the fruit from your seed grow during your own lifespan. We see that with Jeff’s (Millman) 2014 paper already in clinical trials less than 10 years later,” he said.

After graduation, Veronese-Paniagua plans to work in the private sector. He’s interested in working for a pharmaceutical or biotech company to develop tools that can reach patients within his lifetime. He says that he enjoys the concept of seeing the effects of his work. Further down the line, he envisions himself working in an administrative capacity, making scientific decisions within a company.

Veronese-Paniagua understands the importance of maintaining a healthy work-life balance and emphasizes the value of having hobbies and a social circle outside of science. One of his passions outside of the lab is practicing Brazilian Jiu-Jitsu. He has been practicing Jiu-Jitsu at Watson Martial Arts in St. Louis for seven years and says he loves the sport because of the way it slows down the world. “It makes you think a lot about what the movements you have to do against your opponent are. Although to a spectator, it may look fast paced, when you’re on the mats it kind of slows you down, slows your thinking down, and makes you forget about the world because all you’re thinking about is the moves you want to do. It’s a really easy way for me to forget about science,” he said. He also appreciates how the sport tests both his physical and mental abilities. “It’s one of those communities where you can continuously learn from people regardless of their background. I’ve gotten my butt handed to me by people that are in their sixties. And vice versa. I’ve beat people 100 pounds heavier than me. And you can’t do that in other sports for the most part because strength, power, height, age – all those factors come in. But Jiu-Jitsu’s one of those things where you have a little bit more control, and I really like that.”

Additionally, he is dedicated to supporting the younger scientific community, especially in underserved communities. He volunteers with WashU’s Teach Kids Science, a program that brings graduate students to schools and communities in St. Louis, particularly in underserved areas of the city, to provide talks and scientific demonstrations for students in grades K-12. “I think it’s more important when they learn that from people that look like them and showing them that we were in your shoes at some point in life and now we’re here, and it can be you too,” Veronese-Paniagua said. He finds joy in tutoring young scientists and helping them understand the opportunities available to them. “It’s really cool because I’ve spoken to some kids that really like science, but kind of like me when I was in high school, they don’t know what they can do with science.”

Read more about Veronese-Paniagua’s study in bioRxiv here.

Millman Lab Walks for Breakthrough T1D

By Erika Brown – September 30, 2024

Several members of the Millman Lab, along with their families and furry friends, came together for the Breakthrough T1D Walk on Sunday, September 29. This one-mile walk featured additional activities and is designed to raise funds for diabetes research while providing a supportive space for those living with Type 1 Diabetes, their families, and friends. Following a week of rain, most lab attendees sported muddy paw prints on their shirts, evidence of the day’s fun. It was a wonderful opportunity to unite and show our support for the Breakthrough T1D community!

Matt Interviewed by 10x Genomics

By Erika Brown – September 25, 2024

Dr. Matt Ishahak was recently interviewed by 10x Genomics was recently interviewed by 10x Genomics about his groundbreaking work on engineered glioblastoma brain organoids (eGBOs). This innovative model aims to expedite therapeutic development for glioblastoma (GBM), a particularly aggressive brain cancer with a five-year survival rate of less than 5%. 

In the interview, Dr. Ishahak emphasized the advantages of using eGBOs over traditional cancer models. “GBM tumors are super complex,” he explained. “Patients often don’t seek treatment until the cancer is very advanced, meaning their tumors have a high mutational load from the start. Our eGBOs enable insights into early tumor initiation mechanisms. By introducing just a few mutations early on, we can see how that develops into these complex cancer phenotypes often found in patients.”

Check out the whole interview here

Alice Joins the Lab

By Erika Brown – September 25, 2024

The Millman Lab welcomes Alice Smagorinsky to the lab as an undergraduate researcher. Alice is a freshman at WashU from Northbrook, Illinois. She plans to major in biology on the molecular biology and biochemistry track and minor in computer science. Alice has always been fascinated with biology, and her Type 1 diabetes diagnosis in 2017 furthered her interest in a research career. In her free time, Alice loves to hike, work out, watch stand-up comedy, and spend time with her friends. Welcome, Alice!

Mira Gains Citizenship

By Erika Brown – September 20, 2024

Millman Lab member Mira Shunkarova became a US citizen during a ceremony in Belleville,  Illinois last week. Mira immigrated from Kazakhstan with her son and husband in 2021, living in the DC area before moving to her husband’s hometown of O’Fallon a year later. Her husband and in-laws were in attendance at the event. Congratulations, Mira!

New Publication

By Erika Brown – September 4, 2024

Dr. Millman and his colleagues published a comprehensive review article titled “Harnessing Cellular Therapeutics for Type 1 Diabetes Mellitus: Progress, Challenges, and the Road Ahead” in Nature Reviews Endocrinology. This article offers an in-depth analysis of the advancements in cell replacement therapies for treating Type 1 diabetes mellitus (T1DM). The review begins by discussing the current state of pancreatic islet transplantation as a potential cure for T1DM, noting the significant challenges posed by donor scarcity, immune rejection, and the requirement for lifelong immunosuppression.

A major focus of the article is the generation of replenishable β cells from human pluripotent stem cells (hPSCs) as an alternative to donor islets. While these stem cell-derived islets hold significant promise, they face ongoing challenges related to functionality, safety, and scalability. The authors discuss various strategies, including microencapsulation and macroencapsulation, designed to protect transplanted cells from immune rejection without the need for systemic immunosuppression.

The review emphasizes the critical importance of preserving cell viability, engraftment, and functionality through innovative delivery methods. Emerging approaches to localized immunomodulation and reducing the immunogenicity of transplanted β cells are explored, with the goal of achieving long-term immune tolerance and minimizing the need for chronic systemic immunosuppression.

The article also underscores the essential role of animal models in advancing T1DM research, particularly in evaluating cell transplantation and immune modulation strategies. Additionally, the review outlines the challenges and future directions for translating these therapies into clinical practice, emphasizing the need for scalable, safe, and effective products that align with real-world healthcare dynamics.

Overall, this article serves as a roadmap for the development of β cell replacement therapies, advocating for integrated approaches to overcome the technical, regulatory, and clinical challenges that lie ahead.

Check out the article here

Promotion Celebration

By Erika Brown – August 22, 2024

The Division of Endocrinology, Metabolism & Lipid Research hosted a celebratory party on Thursday to honor the promotion of four esteemed faculty members to full professors. Dr. Jeffrey Millman, Dr. Irfan Lodhi, Dr. Maria Remedi, and Dr. Julie Silverstein each received their full professorships and have each made substantial contributions to the field of diabetes research.
Dr. Clay Semenkovich, division chief, addressed attendees, acknowledging the newly promoted professors’ contributions to diabetes research within their careers at WashU.
The event was catered by Across the Board 314, a locally, queer-, and woman-owned charcuterie board company known for its commitment to sustainability.
Congratulations to Drs. Millman, Lodhi, Remedi, and Silverstein!

New Publication in Stem Cells Translational Medicine

By Erika Brown – August 21, 2024

Marlie Maestas, Maggie Bui, and Dr. Millman published a review article in Stem Cells Translational Medicine titled “Recent progress in modeling and treating diabetes using stem cell-derived islets.” The article highlights multiple diabetes-associated diseases that use stem cell-derived islets (SC-islets) for disease modeling and the transplantation of stem cell-derived islets for functional cell therapy. By employing genetic modifications and chemical compounds, researchers can now model diabetes more effectively in vitro, providing valuable insights into disease mechanisms. In addition to detailing these modeling techniques, the review explores strategies for improving SC-islet therapies through immune modulation. By enhancing the body’s acceptance of transplanted islets, these methods aim to boost the efficacy of treatments and offer new hope for patients with diabetes.

Read the article here for more.

Millman Lab Members Place in Local Run

By Erika Brown – August 13, 2024

Left to right: Tai Le, Allison Kelley with Kipper, Ed Sanchez Castro, Marlie Maestas, and Matt Ishahak with Leary

Members of the Millman Lab took a break from their scientific work and participated in the Drink MO Beer Run on Saturday, August 10 at Creve Coeur Park. Participants had the option to run either one mile, a 5K, or a 10K. The event ended with a festival that included beer from local microbreweries, food, and live music.

Some of the lab members took home awards for their placements in the race. In the 10K race, Marlie Maestas secured second place in the female age 20-29 category, and Ed Sanchez Castro claimed the top spot in the male age 20-29 category. This team’s impressive results were further highlighted by Leary, Matt Ishahak’s dog, who placed first in the 5K Doggo group. 

Congratulations to all! 

New Preprint From the Millman Lab

By Erika Brown – August 5, 2024

 

In a recent preprint on bioRxiv from the Millman lab titled “Modeling glioblastoma tumor progression via CRISPR-engineered brain organoids,” Dr. Matthew Ishahak and colleagues explore the use of engineered glioblastoma organoids (eGBOs) to investigate tumor progression in glioblastoma (GBM), an aggressive form of brain cancer. GBM is highly resistant to therapy and exhibits significant intratumoral heterogeneity. Traditional models like genetically modified mice and patient-derived cancer spheroids have limitations in studying early tumor progression and often lack human relevance. In contrast, human pluripotent stem cell-derived brain organoids offer a promising in vitro system to model human neural development and diseases, including cerebral tumors.

The primary objective of this study was to develop eGBOs with subtype-specific oncogenic mutations to investigate the transcriptional regulation and progression of tumors. Researchers used CRISPR-Cas9 to introduce specific GBM-associated mutations into human pluripotent stem cells (hPSCs). To assess the transcriptional and spatial organization of eGBOs, they employed single-cell RNA sequencing (scRNAseq) and spatial transcriptomic analyses. Finally, eGBOs were transplanted into immunodeficient mice to evaluate their ability to form tumors and recapitulate the characteristics of human GBM.

The key findings from the study are that eGBOs with GBM-specific mutations exhibited altered gene regulatory networks, leading to changes in cellular composition and spatial organization. When transplanted into mice, eGBOs formed tumors that mirrored the transcriptional and spatial landscape of human GBM samples. Single-cell trajectory analysis identified dynamic gene expression changes associated with developmental cell states underlying tumor progression. Moreover, eGBO-derived tumors displayed subtype-specific characteristics, demonstrating their utility as models for GBM tumorigenesis.

The study validates the use of engineered cancer organoid models for GBM and underscores their potential in preclinical drug development. eGBOs provide a robust platform for studying GBM tumor progression and investigating new therapeutic approaches. This model system helps bridge the gap between preclinical findings and clinical applications, potentially leading to the development of more effective treatments for GBM. By offering a more human-relevant model for understanding GBM progression, eGBOs hold promise for advancing the research and treatment of this formidable disease.

About the Researchers

This research was conducted by a team of scientists, including Dr. Matthew Ishahak, Dr. Jeffrey Millman, Dr. Albert Kim, and their colleagues at Washington University School of Medicine.

For further details on the study, the preprint publication can be accessed here.

Meet the Researcher: Marlie Maestas

By Erika Brown – August 2, 2024

Marlie Maestas, a fifth-year graduate student in the Millman Lab, recently published her first first-authorship in Nature Communications. The study, titled Identification of unique cell type responses in pancreatic islets to stress, detailed the responses of different pancreatic islet cell types to endoplasmic reticulum and inflammatory stress. Maestas and her colleagues used single-cell RNA sequencing to detect stress’s impact on gene expression in each cell type and demonstrated that each type responds differently. The study indexed these responses and identified beta-cell-specific responses. Additionally, Maestas, Millman Lab and Urano Lab used their findings to identify the candidate gene CIB1 as a potential regulator of beta cell function.  

“This study was designed to utilize multiplexed sequencing to understand the effects of different types of cell stress and reduce the variability due to multiple sequencing runs,” Maestas said. “Previous studies have investigated the compounds we have tested here; however, we noticed that these studies did not investigate cell-type-specific responses, leading us to design this study.”

The findings provide a detailed map of how pancreatic cells react to stress, offering insights that could lead to new therapeutic strategies. By targeting specific stress pathways, it may be possible to protect β-cells from damage and improve the overall health of pancreatic islets in diabetic patients. 

Maestas received her Bachelor of Science in Biology from New Mexico State University and says she picked Washington University for graduate school because of the community. “When I came for my interview, I really liked all of the people and I felt like I would really be a part of a community,” she said. In 2021, Maestas joined the Millman Lab as a doctoral student in developmental, regenerative, stem cell biology. Although she initially joined the lab because of the people and the environment, she really enjoys the translational aspects of the lab and how much of an impact the studies have on diabetes research. Having family and friends who have diabetes has made her even more interested in the research.  

After graduate school, Maestas plans to work in the biotechnology industry, designing new products or medicine to continue helping patients. She talked about shadowing a physician assistant during her undergraduate studies. “Every day she gave patients new medicines to try to see if they would help. While shadowing, I realized I wanted to be the person involved in understanding and creating new medicines for people.”

When she’s not working in the lab, Maestas likes to travel, hang out with her friends, and get lost in a good book. Her favorite destination so far is the Philippines, where she loved the people, food, and landscapes.  

Read more about Maestas’s study in Nature Communications here.  

James Joins the Lab

By Erika Brown – July 29, 2024

The Millman Lab welcomes James Lu to the lab as a post-baccalaureate scholar in the Division of Cellular and Biomedical Research and Medicine (DCBRM). James, a recent graduate of the University of Oklahoma, holds both a B.S. in Biological Sciences and a B.A. in Spanish Linguistics and Literature, having completed his studies in May 2024. James is from Tulsa, OK, and is looking forward to learning more in the lab to further his interests in advancing treatment and management strategies for chronic illnesses, particularly diabetes and obesity. Outside of lab, James enjoys pickleball, exploring local cuisine, and experimenting with cooking. Welcome, James!

New Preprint From the Millman Lab

By Erika Brown – July 24, 2024

In a recent preprint from the Millman Lab titled “Coxsackievirus B infection invokes unique cell-type specific responses in primary human pancreatic islets,” Daniel Veronese-Paniagua and colleagues have shed new light on the intricate mechanisms through which Coxsackievirus B3 (CVB) may trigger type 1 diabetes (T1D). Published as a preprint in bioRxiv, the study utilized single-cell RNA sequencing to uncover distinct responses within pancreatic islet cell types—specifically β, α, and ductal cells—following CVB infection.

CVB has long been suspected to play a role in the onset of T1D, an autoimmune condition where the immune system attacks insulin-producing β cells in the pancreas. Veronese-Paniagua’s study provides crucial insights into how this virus induces transcriptional changes that disrupt cellular functions crucial for maintaining glucose homeostasis.

Key Findings:

  1. Cell-Specific Responses: The research identified unique transcriptional responses in different cell types within pancreatic islets. β cells, critical for insulin production, showed significant changes linked to mitochondrial dysfunction, immune responses, and inflammation pathways upon CVB infection.
  2. Impact on Mitochondrial Function: CVB infection was found to disrupt oxidative phosphorylation pathways in β cells, suggesting a direct mechanism through which viral infection impairs energy production and cellular function.
  3. Role of Long Non-Coding RNA: The study highlighted the upregulation of MIR7-3HG, a long non-coding RNA, in β cells with high viral loads. Knockdown experiments demonstrated that reducing MIR7-3HG levels could potentially mitigate viral protein expression and apoptosis in β cells, pointing to a novel therapeutic target.
  4. Implications for Therapy: These findings offer promising avenues for therapeutic intervention aimed at protecting β cells from viral-induced damage and subsequent autoimmune attacks in individuals predisposed to T1D.

Veronese-Paniagua emphasized that understanding the molecular pathways activated by CVB in pancreatic islet cells is crucial for developing targeted therapies that could potentially prevent or mitigate the progression of T1D in susceptible individuals.

This study underscores the complex interplay between viral infections, cellular responses, and autoimmune diseases like T1D. As research continues to unravel these connections, there is hope for future treatments that could preserve pancreatic function and improve outcomes for individuals at risk of developing diabetes.

Implications for Diabetes Treatment

This preprint publication marks a significant milestone in advancing our understanding of the link between viral infections and the development of T1D, offering new avenues for clinical research and treatment development.

About the Researchers

This research was conducted by a team of scientists including Daniel Veronese-Paniagua, Dr. Jeffrey Millman, Dr. Hubert Tse of the University of Kansas Medical Center, and their colleagues at Washington University School of Medicine and University of Kansas Medical Center.

For further details on the study, the preprint publication can be accessed here.

Contributions to the 84th Scientific Sessions

By Courtney Casteel – July 24, 2024

Many members of the Division of Endocrinology, Metabolism and Lipid Research participated at the American Diabetes Association‘s 84th Scientific Sessions, which took place in Orlando, Florida from June 21-24. Those members include Esmeralda Castelblanco Echavarria, PhDKai Jones, MDJeffrey R. Millman, PhDMax C. Petersen, MD, PhDR. Mei Zhang, MD; and Wei Zhang, PhD.

As the world’s largest meeting on diabetes, the sessions have welcomed colleagues and experts from over 115 countries to promote collaboration and scientific advancement in the field. The sessions encompassed eight theme areas that allowed attendees to learn about the latest scientific findings, groundbreaking research presentations, and to experience the exhibit and poster halls with the intention of accelerating the progression toward diabetes prevention and finding a cure.

Division Participants

Esmeralda Castelblanco Echavarria, PhD
Esmeralda Castelblanco Echavarria, PhD

Poster Presentation 
Theme Area: Clinical and Preclinical Pancreas Immunology and Islet function
Session: Beta Cell Signal Transduction  
Restoring beta-cell Mass and Identity in KATP-Induced Neonatal Diabetes – The Synergy of Autophagy and Intermittent Fasting   

Kai Jones, MD 

Oral Presentation 
Theme Area: Clinical Diabetes/Therapeutics 
Session: “New Technology—What’s New?” 
Breath Acetone Correlates with Capillary Beta Hydroxybutyrate in Type 1 Diabetes

Jeffrey R. Millman, PhD 

Oral Presentation 
Theme Area: Immunology/Beta-Cell Replacement  
Session: The “Barrier Reef”—Overcoming Hurdles to Beta-Cell Replacement Therapies  Overcoming Islet Scarcity through In Vitro Differentiation of Human Pluripotent Stem Cells 

Dr. Jeffrey Millman (second from the left) joined other panelists at ADA 84th Scientific Sessions.

Dr. Millman also participated in an expert panel discussing the heterogeneity of type 1 diabetes (T1D), covering topics such as beta cell pathology, T1D prevention, and insulin replacement. He was one of the experts selected to later present a summary of the panel discussion. In addition, Dr. Millman joined a public panel on the subject and will be co-authoring a review article with his co-panelists to further disseminate their findings.

Max C. Petersen, MD, PhD 

Poster Presentation 
Theme Area: Insulin Action/Molecular Metabolism  
Session: Metabolite Transport and Molecular Metabolism 
Effect of Dapagliflozin on Blood and Breath Ketones During Supervised Insulin Withdrawal in Adults with Type 1 Diabetes 

Oral Presentatio
Theme Area: Obesity/Integrated Physiology  
Session: Risk Factors Reimagined—Beyond Obesity in Metabolic Risk  
Plasma Lipidome in People with Insulin-Sensitive and Insulin-Resistant Obesity 

Mei Zhang, MD
R. Mei Zhang, MD 

Poster Presentation 
Theme Area: Behavioral Medicine, Clinical Nutrition, Education, and Exercise  
Session: Type 2 Diabetes and Exercise—Where Do We Stand?  
Acute Hyperglycemia Induces Human Podocyte Apoptosis by Increasing Monocyte Release of TNF-a Through ER Stress/ROS Activation of ADAM17/iRhom2 Expression 

Wei Zhang, PhD 

Oral Presentation  
Theme Area: Insulin Action/Molecular Metabolism  
Session: Novel Regulators of Insulin Action and Insulin Sensitivity 
Depalmitoylation Inhibition Improves Glucose Tolerance by Promoting Endothelial Insulin Transcytosis 

Additionally, Dr. Zhang was named a recipient of the Young Investigator Award and received one of the top scores within the program.

Millman Lab Participates in Neighborhood Cleanup

By Erika Brown – July 13, 2024

Members of the Millman Lab and their families rolled up their sleeves and joined forces with local residents for a neighborhood cleanup in Normandy, MO on Saturday, July 13. This event was organized as part of earthday365‘s Environmental Justice Days of Action and co-hosted by Metropolitan Congregations United (MCU).

Environmental Justice Days of Action are community service focused days aimed at addressing food apartheid, litter, and illegal dumping typically in poor or marginalized communities. This cleanup focused on addressing litter and illegal dumping in the underserved community of Normandy, a city in St. Louis County.

The event concluded with a group discussion about how policy and education can help pave the way for a cleaner, healthier Earth. With continued efforts like these, organizers hope to inspire ongoing environmental stewardship and community involvement beyond Environmental Justice Days of Action.

New Publication in Nature Communications

By Erika Brown – July 3, 2024

Recent research published in Nature Communications sheds light on how different cell types in the pancreas respond to stress, revealing potential new targets for diabetes treatment. The study, led by Marlie Maestas of the Millman laboratory at Washington University School of Medicine, focuses on the pancreatic islets, which contain cells crucial for regulating blood sugar.

Diabetes, a chronic condition affecting millions worldwide, involves the malfunction or death of pancreatic β-cells, which produce insulin. Insulin is essential for maintaining normal blood sugar levels. The study investigates how these cells, along with other cell types in the pancreatic islets, respond to two major stressors: endoplasmic reticulum (ER) stress and inflammatory stress.

Key Findings:

  1. Cell-Specific Stress Responses: The researchers used advanced single-cell RNA sequencing to analyze how different cell types in the pancreas react to stress. They found that β-cells, α-cells, and ductal cells have the most significant responses to stress. β-cells, responsible for insulin production, showed extensive changes in gene expression when exposed to stress.
  2. ER Stress and Inflammatory Stress: ER stress occurs when the ER, a cell structure involved in protein folding, becomes overwhelmed with misfolded proteins. This can happen due to various factors, including high blood sugar and inflammation. The study identified that β-cells under ER stress had increased expression of genes related to cell death, while α-cells (which produce glucagon) showed increased expression of survival genes.
  3. Potential Therapeutic Targets: One of the significant findings was the role of a gene called CIB1, which was upregulated in stressed β-cells. When the researchers modified stem cell-derived islets to overexpress or knock down CIB1, they observed changes in insulin secretion and cell survival. This suggests that CIB1 could be a potential target for developing new diabetes treatments.
  4. Differences Between Cell Types: The study also highlighted the differences in how various pancreatic cell types respond to stress. For instance, α-cells and ductal cells exhibited different patterns of gene expression under stress compared to β-cells. Understanding these differences is crucial for developing targeted therapies that address the specific needs of each cell type.

Implications for Diabetes Treatment:

The findings from this study provide a detailed map of how pancreatic cells react to stress, offering insights that could lead to new therapeutic strategies. By targeting specific stress pathways, it may be possible to protect β-cells from damage and improve the overall health of pancreatic islets in diabetic patients.

About the Researchers:

This research was conducted by a team of scientists including Marlie Maestas, Dr. Jeffrey Millman, Dr. Fumihiko Urano, and their colleagues at Washington University School of Medicine. Their work continues to advance our understanding of diabetes and pave the way for innovative treatments.

For more detailed information, you can access the full study here.

References: Maestas, M. M., Ishahak, M., Augsornworawat, P., Veronese-Paniagua, D. A., Maxwell, K. G., Velazco-Cruz, L., Marquez, E., Sun, J., Shunkarova, M., Gale, S. E., Urano, F., & Millman, J. R. (2024). Identification of unique cell type responses in pancreatic islets to stress. Nature Communications, 15:5567. https://doi.org/10.1038/s41467-024-49724-w.

Dr. Millman Promoted

By Erika Brown – July 1, 2024

Dr. Millman received a promotion to full Professor today. Congratulations, Dr. Millman!

Dr. Millman Presents at ADA

By Erika Brown – July 1, 2024

Jeffrey Millman, PhD, presented at the American Diabetes Association’s (ADA) 84th Scientific Sessions this June in Orlando, FL. This prestigious meeting convenes experts in diabetes research, treatment, and care to share the latest findings and discuss advancements in the field. It serves as a crucial platform for exchanging new insights, fostering collaborations, and shaping the future of diabetes management worldwide.

In his presentation, Dr. Millman provided an update on the progress in creating and understanding stem cell-derived islets. He highlighted his lab’s latest work, which includes sophisticated bioinformatic modeling of the entire differentiation process at a single-cell level, both transcriptionally and epigenetically.

On Thursday, June 20, Dr. Millman participated in an expert panel discussing the heterogeneity of type 1 diabetes (T1D). The panel covered topics such as beta cell pathology, T1D prevention, and insulin replacement. Dr. Millman was also one of the experts selected to present a summary of the panel discussion to the meeting attendees on Monday, June 24. Additionally, he joined a public panel to delve deeper into the heterogeneity of T1D. Following these discussions, Dr. Millman will be co-authoring a review article with the other panel participants to further disseminate their findings to the broader scientific community.

Tai Le Joins the Lab

By Erika Brown – June 18, 2024

Tai Le joined the lab as a Research Technician this week. He recently obtained his B.S. in Cell and Molecular Biology from Missouri State University, and plans on pursuing an M.D./Ph.D. in the future. Outside of lab, Tai enjoys cooking, writing, and reading anything relating to literature and philosophy. Welcome, Tai!

Dr. Millman Featured in DOM News

May 22, 2024

Dr. Millman was the subject of an article written recently for the Department of Medicine. The article spotlighted the research at the Millman Lab and some of Dr. Millman’s background in diabetes research. Read the article here

Dr. Ishahak at Fellows’ Research Day

May 2, 2024

Dr. Matthew Ishahak presented at the division Fellows’ Research Day. His talk was titled “Single-Cell Multiomic Atlas Elucidates Cell Fate Specification in Stem Cell-derived Islets.” Fellows’ Research Day is a twice-per-year opportunity for fellows in the department to showcase their research.

Millman Lab at the Dream Gala St. Louis

April 18, 2024

Members of the Millman Lab and their families attended the 2024 JDRF Dream Gala St. Louis on Saturday. The gala is a fundraising event for community and corporate leaders in the T1D community benefiting the JDRF Kansas & Missouri chapter.

Clinical Trial Featuring Millman Lab Research Gets Update

April 15, 2024

Last week, Amylyx Pharmaceuticals released interim data from the ongoing HELIOS clinical trial that features Millman Lab research. The trial is using AMX0035 to improve pancreatic function and glycemic control in Wolfram Syndrome patients. The Millman Lab previously used SC-islets that were made from patients with Wolfram Syndrome to do a preclinical evaluation of this compound. The interim data showed that patients had an increase in C-peptide and beta cells had more rapid responses to glucose challenge, which was unexpected due to disease progression. Additionally, most patients had a decrease in A1c and an increase in time in range.  There were other benefits as well reflected in the summary graphic above. Read more about the preclincal study here and the update here

Dr. Millman Featured On The Sugar Science Podcast

March 5, 2024

 

Dr. Millman was featured in the “Ask the Expert” segment of The Sugar Science podcast. He discussed using single-cell sequencing to understand the cellular complexity of SC-Islet identity.

Ella and Liam Join the Lab

February 19, 2024

 

Ella Hanson and Liam Oiknine joined the lab as trainees this month. Ella is in the B.S./M.S. Biomedical Engineering program at WashU and Liam is a Freshman at WashU, studying Computer Science and Biology. Welcome, Ella and Liam!

New Paper in BMC Genomics

January 24, 2024

 

Mason Schmidt (former postbacc student), Matt Ishahak, Punn Augsornworawat (former Ph.D. student) and Dr. Millman published a paper in BMC Genomics. The publication reveals comparisons of SC-islets, fetal islets, and adult islets using single-cell sequencing datasets to characterize the transcriptional identity of each. The team’s analysis revealed that SC-β cells share a core β-cell transcriptional identity with human adult and fetal β-cells, however SC-β cells possess a unique transcriptional profile. Read the open-access article here

2023 Holiday Party

December 12, 2023

The Millman Lab celebrated the holidays and the end of the year with an afternoon at Topgolf in St. Louis. Trainees and staff played a few games and white elephant gifts were exchanged. 

Happy holidays from the Millman Lab!

Millman Lab Recognized at the COVID-19 Awards

November 28, 2023

Drs. Millman and Hogrebe were recognized at the WashU COVID-19 Awards. The COVID-19 Awards recognize outstanding individuals for their work and contributions in the Department of Medicine during the pandemic. 

Dr. Millman was awarded the COVID Star Award and Dr. Hogrebe was awarded the COVID Rising Star Award. 

Congratulations, Drs. Millman and Hogrebe!

Millman Lab Receives Green Lab Certification at Green Carpet Awards

November 21, 2023

 

The Green Carpet Awards are an annual award ceremony honoring WashU labs and offices that certified as Sustainability Champions through the WashU Sustainability office. The Millman Lab was certified at the Gold level for its efforts to conduct research in more sustainable ways. Erika Brown (back right) attended the awards as the lab’s Green Lab representative. Read more about the awards here and the Green Labs program here

Millman Lab Participates in 2023 Diabetes Day Symposium

November 9, 2023

 

The WashU Diabetes Research Center hosts an annual diabetes symposium in honor of World Diabetes Day, which falls on November 14. The event brings together DRC scientists and their trainees to showcase the latest developments in diabetes research. During the symposium, Dr. Lori Sussel, Research Director of the Barbara Davis Center for Diabetes at the University of Colorado, delivered a lecture. Danny Veronese Paniagua, Ed Castro-Sanchez, Kameron Bradley, Marlie Maestas, and Matt Ishahak presented posters throughout the day-long event.

Dr. Millman Speaks at 50th Kilo Diabetes Symposium

November 4, 2023

Dr. Millman spoke at the 50th annual Kilo Diabetes Symposium on Saturday. He gave a talk about Cell Therapy for T1D and participated in a panel discussion on T1D Prevention and Reversal.

The Kilo Diabetes Symposium is a national forum for leaders in the field to educate the medical community about research findings and good clinical practice in diabetes, endocrinology, and cardiovascular diseases.  

Millman Lab at 2023 JDRF One Walk

October 22, 2023

Several members of the Millman Lab and their families came out to the 2023 JDRF One Walk. The one-mile walk is a fundraiser for diabetes research and a way for those living with T1D and their friends and families to come together and support the fight for a cure. It was a beautiful day to spend together and support our friends at JDRF! 

Matt and Kameron Present at BMES 2023

October 16, 2023

Dr. Matt Ishahak and Kameron Bradley spent last week at the 2023 Biomedical Engineering Society (BMES) Annual Meeting in Seattle, WA. Kameron presented a poster on his hypoxia work and Matt gave a talk on the lab’s HIRN catalyst project.  Matt also received an award from the Engineering Endocrine Tissue Special Session. 

Millman Lab at Environmental Justice Day of Action

September 30, 2023

Dr. Millman, Charlotte Millman, Alexa Wagner, Matt Ishahak, and Erika Brown participated in a neighborhood cleanup in O’Fallon Park in North City St. Louis on Saturday. The cleanup was part of St. Louis Environmental Justice Days of Action, an initiative to address environmental justice issues such as illegal dumping and food apartheid, which is led by earthday365 and North Newstead Association. It was a great day to help out the local community!

Alexa Joins the Lab

September 25, 2023

Alexa Wagner joins the lab as a Research Assistant. Welcome, Alexa!

Dr. Ishahak Wins Award

September 25, 2023

Dr. Matt Ishahak received the Distinguished Postdoctoral Scholars award from the Center of Regenerative Medicine. This program is designed to develop highly trained individuals who can produce impactful research in regenerative medicine through an interdisciplinary training plan. Congratulations, Matt!

Drs. Millman and Ishahak Attend HIRN Annual Meeting

September 25, 2023
 

Dr. Millman and Dr. Matt Ishahak attended the Human Islet Research Network (HIRN) annual meeting last week. They both presented at the meeting and Dr. Millman participated in the hypoimmune islet panel.

Millman Lab at Environmental Justice Day of Action

August 12, 2023
 

Dr. Millman, Charlotte Millman, Ed Castro-Sanchez, Marlie Maestas, and Erika Brown participated in a neighborhood cleanup in Jennings, MO on Saturday. The cleanup was part of St. Louis Environmental Justice Days of Action, an initiative to address environmental justice issues such as illegal dumping and food apartheid, which is led by earthday365. It was a great day to spend some time together and do some good for the community!

Cam’s Last Day

August 4, 2023
 

The Millman Lab said goodbye to Cameorn Banks on Friday with lunch from Lona’s Lil Cafe. Cam is heading to a Ph.D. program at the University of Minnesota in the fall where he will study within the Microbiology, Immunology, and Cancer Biology (MICaB) program. Good luck, Cam; we will miss you!

Veronica’s Last Day

August 2, 2023
 

Veronica Lee had her last day of her summer research period in the lab on Wednesday. She will continue her undergraduate study at WashU. Good luck, Veronica!

Diana Promoted

July 24, 2023
 

Diana Hernandez has been promoted to Senior Research Technician. Congratulations, Diana!

Camryn Gives Talk at uSTAR Closing Symposium

July 20, 2023
 

Camryn Moore spoke on her research in the Millman Lab at the uSTAR Summer Scholars Program Closing Symposium. The talk was entitled “CRISPR Validation and Functional Analysis of Hypoxic and Normoxic Stem Cell-Derived Islets.” Great job, Camryn!

JDRF Kids Visit Millman Lab

July 10, 2023
 

The Millman Lab had a recent visit from the local chapter of JDRF, where we had the pleasure of hosting several families with children affected by T1D. Guests were given a tour of the lab with talks by Millman Lab members. A reception followed with pipette racing, a sink or float experiment, and a photo booth. Thank you to Millman Lab volunteers, JDRF, and the families!

Lab Certifies Gold With WashU Green Labs

July 5, 2023
 

The Millman Lab has been certified gold with WashU’s Green Labs Program. Read More about some of our sustainability efforts here!

Mason Farewell Lunch

June 26, 2023
 

The Millman Lab said goodbye to Mason Schmidt on Monday with lunch from Gioia’s Deli. Mason is heading to a Ph.D. program at Duke in the fall where he will study within the Developmental and Stem Cell Biology program. Good luck, Mason; we will miss you!

Dr. Millman Speaks at 2023 Endocrine Society

June 20, 2023
 

Dr. Millman spoke at ENDO 2023 in Chicago over the weekend. His talk was featured at the plenary session on “The Future of Endocrine Therapies: Personalized Organoids And Gene Editing – Is This The Real-Life or Just Fantasy?”. 

Millman Lab Presents at ISSCR

June 19, 2023
 

Kameron Bradley, Danny Veronese Paniagua, Matt Ishahak, Diana Hernandez, and Marlie Maestas attended the 2023 International Society for Stem Cell Research (ISSCR) meeting in Boston, MA. They presented posters on the latest research from the lab.

Millman Lab Featured in WashU News

June 9, 2023
 

The Millman Lab’s latest publication in Nature Cell Biology was featured in a press release by WUSM News. The article explains the study, which was on creating improved stem cell-derived beta cells through machine learning and computational methods. Read the article here

Camryn and Veronica Join the Lab

June 5, 2023
 

Camryn Moore and Veronica Lee both join the lab as undergraduate trainees. Camryn is with the WashU U-Star Summer Scholar Program and Veronica is with the WashU Amgen Scholars Program. They will be mentored by Kameron Bradley and Marlie Maestas respectively. Welcome, Camryn and Veronica!

Allison Joins the Lab

June 1, 2023
 

Allison Kelley joins the lab as a Research Technician. Welcome, Allison!

New Paper in Nature Cell Biology

May 15, 2023
 
Several current and former members of the Millman Lab authored a detailed multiomic study of stem cell-derived islets (SC-islets) & natural islets at single-cell resolution. This study identified specific chromatin regulators that can enhance or harm SC-islet identity. Overexpression of CTCF increased intestinal and decreased islet identity while knockdown of ARID1B increased islet and decreased off-target/progenitor identities.
 

Link to the open access article here.  

Diana Graduates

May 10, 2023
 
Diana Hernandez graduated last week with her Master’s in Microbiology and Cell Science from the University of Florida. Congratulations, Diana!
 

Ed Joins the Lab

May 9, 2023
 
Ed Sanchez Castro joins the lab as a doctoral student from the Developmental, Regenerative, and Stem Cell Biology division. Welcome, Ed!

New Paper in Nature Biotechnology

May 8, 2023
 
Drs. Hogrebe and Millman co-authored a paper in Nature Biotechnology demonstrating islet hypoimmunity using CRISPR editing to knockout HLA & overexpress CD47.

Link to the open access article here.  

Lab Participates in Park Cleanup

May 6, 2023
 
 

Members of the Millman Lab and their families participated in a cleanup of O’Fallon Park in St. Louis. The cleanup was part of St. Louis Environmental Justice Days of Action, an initiative to address environmental justice issues such as illegal dumping and food apartheid. It was a great day to spend some time together and do some good for the community. 

New Paper in Cell Stem Cell

May 4, 2023
 
Drs. Hogrebe, Ishahak, and Millman published a review article in Cell Stem Cell highlighting recent advances in the generation and characterization of highly functional islets from stem cells for diabetes as well as strategies to ensure graft viability & safety after transplantation. 

Link to the open access article here.  

Millman Lab Lunch

May 1, 2023
 
The lab gathered at The Gramophone on Friday to wish Chandler farewell as well as to celebrate Aining passing her Master’s thesis defense and Mira joining the lab. Congratulations to Aining and Mira! We’ll miss you, Chandler!

Dr. Millman Study Featured on JDRF News

April 28, 2023
 
Dr. Millman’s study with Sana Biotechnology was featured on JDRF’s website. The study was on avoiding immune system attacks and stabilizing blood glucose levels without immunosuppressants. Check out the article here

Aining Passes Masters Thesis Defense

April 26, 2023
 
Masters student Aining Fan successfully defended her BME MS thesis.  She will be moving on to the BME PhD program at UCSD. Congratulations, Aining!

Chandler Accepts Position at Bayer

April 21, 2023
 
Dr. Chandler Est has accepted a position at Bayer as a Protein Scientist where he’ll be working on recombinant protein expression, purification, and characterization. Congratulations, Chandler! We’ll miss you!

Mira Joins the Lab

April 13, 2023
 
Dr. Mira Shunkarova joins the Millman Lab as a Research Assistant. Welcome, Mira!

Mason Awarded NSF Fellowship

March 30, 2023
 
Mason Schmidt is a recipient of an NSF Graduate Research Fellowship Program (GRFP) fellowship to support his future graduate studies! He has also accepted a position in Duke’s Developmental and Stem Cell Biology graduate program, which he will begin in the fall. Congratulations, Mason!

Punn Defends Thesis

March 28, 2023
 
Doctoral student Punn Augsornworawat successfully defended his thesis entitled, “Development and Maturation of Human Pluripotent Stem Cell Derived Pancreatic Islets.” Congratulations Dr. Augsornworawat!

Matt Accepts Position On WashU Council

March 17, 2023
 
Dr. Ishahak has been accepted to a position on the CRM (Center of Regenerative Medicine) Early Career Executive Council. The council collaborates with staff and directors of the CRM to advise on the needs of the in-training members of the Center and design and led the implementation of yearly CRM networking and training events. Congratulations, Matt!

Danny Receives Award

March 17, 2023
 
Daniel Veronese Paniagua has been invited to attend the 41st Annual Hamburger Lecture, at which he will be awarded the Viktor Hamburger Award for Best Student Oral Presentation at DRSCB (Developmental, Regenerative, and Stem Cell Biology) Retreat. Congratulations, Danny!

Cameron Accepted Into Graduate School

March 17, 2023
 
Cameron Banks has accepted a position in the University of Minnesota’s Microbiology, Immunology, and Cancer Biology (MICaB) graduate program! He is also a recipient of the University of Minnesota Medical School Graduate Fellowship. Congratulations, Cameron!

JDRF Visit

March 1, 2023
 
The lab was happy to host a visit by our friends at the Kansas & Missouri Chapter of JDRF. It was great to share how we conduct our research on stem cell-derived islets for fighting T1D!

Nathaniel Hogrebe Promoted

February 1, 2023
 
Dr. Hogrebe has been promoted to Instructor in Medicine. Congratulations, Dr. Hogrebe!

Lab Holiday Party

December 7, 2022
 
Members of the lab celebrated the holidays together at Urban Chestnut. There was a white elephant gift exchange and superlatives were given out.
 
2022 was a great year and we’re looking forward to an amazing 2023! 

Nathaniel Hogrebe Presented at GESC Symposium

December 1, 2022
 

Dr. Nathaniel Hogrebe spoke at the GESC Symposium on Differentiation. He spoke about the lab’s research on stem cell derived islets for the treatment of diabetes.

Erika joins the Millman lab

November 28, 2022
 
We welcome Erika Brown to the Millman lab as a Grant Assistant to Dr. Millman. 

Punn Augsornworawat receives award on Diabetes day

November 10, 2022
 
Punn Augsornworawat presented at the Diabetes Day conference on the use of single-cell technologies to reveal transcriptional regulators in pancreatic islets. He was awarded the best basic science presenter award. 

Daniel Veronese-Paniagua at SACNAS NDiSTEM

October 27, 2022
 
Daniel Veronese-Paniagua of Millman lab attends the SACNAS NDiSTEM 2022 conference in San Juan, Puerto Rico. He was awarded for the best poster presentation on the effects of diabetes associated viral infection on human islets. 

Punn Augsornworawat, Matthew Ishahak, and Aining Fan at BMES 2022

October 13 2022
 
 
Punn Augsornworawat, Matthew Ishahak, and Aining Fan presented at the 2022 BMES Annual Meeting in San Antonio, TX. Punn and Matthew gave platform presentations and Aining Fan gave poster presentation on novel works on pancreatic islet and brain organoid development. 
 

Punn Augsornworawat at TERMIS-AP 2022 South Korea

Octobre 5, 2022
Punn Augsornworawat participated and presented at TERMIS-AP 2022 for regenerative medicine in Jeju, South Korea. He was given the best oral presentation award for his talk on “Single-cell multiomic profiling identifies novel regulators of stem cell derived β-cell differentiation and maturation”. 

New paper on Advanced Materials Technologies

October 3, 2022
Millman and Gale publish in Advanced Materials Technologies – “A Predictive Oxygen Durability Model to Analyze Oxygen Consumption of Insulin Producing Cells Encapsulated Within a Highly Oxygenated Hydrogel”

New paper on JCI Insight

September 22, 2022
Millman, Maxwell, and Augsornworawat publish new paper on JCI Insight entitled “Multidimensional analysis and therapeutic development using patient iPSC–derived disease models of Wolfram syndrome”.

Millmab lab at DBBS Retreat

September 6, 2022
Veronese-Paniagua, Maestas and Schmidt participated and presented at the 4th Annual DRSCB Program, Developmental Biology Department and Center of Regenerative Medicine Joint Retreat. Veronese-Paniagua was awarded for the best student oral presentation.

Matthew Ishahak presented at UNITE

August 29, 2002
Dr. Ishahak presents at the BME UNITE Seminar Series titled  “Engineering Organoid Microsystems to Model Human Physiology and Disease”
 

Danny is part of E4B

August 28, 2022

Daniel Veronese Paniagua is accepted into the E4B Entrepreneurship program. He will be exploring entrepreneurship in biomedical science.
 

Jeffrey Millman receives HIRN grant

August 25, 2022
Millman receives the HIRN Catalyst Initiative funding and is invited to the Consortium on Human Islet Biomimetics (CHIB). His research focus for this funding is on “Epigenomic Engineering of Stem Cell-Derived Pancreatic Cells”.

Punn Augsornworawat featured on The Scientist

August 19, 2022


Punn Augsornworawat was featured atThe Scientist Symposium “Understanding the stem cell niche, one cell at a time” , where he presented his work on “Stem cell derived islet development and maturation at single-cell resolution”

Jeffrey Millman named Mallinckrodt Scholar

August 1, 2022
 
Dr. Millman named the 74th Mallinckrodt Scholar, with funding of $100,000 for four subsequent years.
 
 

Dr. Millman on AP news

July 19, 2022

Jeffrey Millman, PhD. was recently interviewed by the Associated Press on growing stem cells in space. This topic covers interesting areas on whether or not stem cells can grow in the zero gravity condition. Check out the this link here. 

News link

Matthew awarded by NIH

June 24, 2022
 
Matthew Ishahak was selected for the NIH National Research Service Award (NRSA) postdoctoral fellowship on the Diabetes and Related Metabolic Diseases Training grant in the Division of Endocrinology at Washington University School of Medicine (5 T32 DK007120)

Millman lab team presents at ISSCR 2022

June 18, 2022

Millman lab members Augsornworawat, Ishahak, Maestas, Veronese-Paniagua, Schmidt, and Marquez presented at the International Society for Stem Cell Research (ISSCR) in San Francisco, CA. Veronese-Paniagua gave platform presentation and Augsornworawat, Ishahak, Maestas, Schmidt, and Marquez gave poster presentation on novel works on pancreatic islet and brain organoid development and modeling. 

Mason joins dkNET Summer of Data Student Program

June 2, 2022

Mason Schmidt, our lab’s postgraduate researcher, joins the 2022 dkNET Summer of Data Student Program and is awarded a scholarship for the program. Congratulations! 

Julia Miller graduates from Washu!

June 1, 2022

Julia Miller graduated with a Bachelor of science in biomedical engineering this summer. She has been actively working with the Millman Lab on engineering Stem cells to produce pancreatic islets. Congratulations!

Augsornworawat wins BME research award

May  11, 2022

Punn Augsornworawat received the Biomedical Engineering (BME) Outstanding Research Award on May 2, 2022. His works are focused on developing methodologies to generate pancreatic islets from stem cells and utilizing single-cell technologies to study islet development and β-cell maturation. 

News Link

Maggie joins the Lab!

April  4, 2022

We are proud to announce that Maggie Bui, MSTP student, will be joining our lab to work on her PhD in islet development and biology. 

New publication on Stem Cells Translational Medicine

March  21, 2022

We are proud to share our new publication “Differential Function and Maturation of Human Stem Cell-Derived Islets After Transplantation”. This study explores different transplantation strategies for SC-islets in diabetic mice. Link

“A Possible Cure for Diabetes”

February 1, 2022

Dr. Millman is featured in Eureka’s Podcast “A Possible Cure for Diabetes”. Check out on our research highlights and current progress in Diabetes cure. Link

Millman lab welcomes new members!

Janurary 20, 2022

We are excited to welcome 2 new members to the Millman Lab. Kameron joined us as a doctoral student from the department of biomedical engineering. Aining, from the department of biomedical engineering, joined us a Masters student. Welcome! 

Dr. Millman was interviewed for an article in IEEE Pulse

November 9, 2021

Dr. Millman was interviewed for an article in IEEE Pulse about the promises and challenges of stem cells for diabetes cell replacement therapy. Check out the article here!

Link

Julia Receives Future Leaders in Chemical Engineering Award

November 8, 2021

We are proud to see Julia Miller, an Undergraduate student in Biomedical Engineering who has been working with us, receiving a Future Leaders in Chemical Engineering award! Julia’s work is on genetic engineering of Stem cell derived Islets.  Congratulations Julia!

Dr. Est joins Millman lab!

October 18, 2021

Millman lab welcomes new Post-doctoral fellow Dr. Chandler Est! Chandler will be studying Islet differentiations using genetic engineering tools and developing new approaches to investigate diabetes.  

Millman lab presents at BMES 2021 in Orlando

October 15, 2021

Last week, Punn Augsornworawat, Matthew Ishahak, and Julia Miller gave oral presentations at the 2021 BMES conference in Orlando, Florida. Each presented their Stem cell and Diabetes research work. 

Dr. Millman is featured on an interview with Nature

September 29, 2021

Nature Publishing Group interviewed Dr. Millman on the feasibility and current efforts in scaling and manufacturing cells for cell replacement therapies. The interview is featured in “Stem-cell start-ups seek to crack the mass-production problem”

Link

Matthew receives NIH LRP award

August 6, 2021

Big congratulations to Dr. Ishahak for receiving the NIH LRP award from the National institute of Diabetes and Digestive and kidney diseases (NIDDK).

Published in Nature Protocols!

August 3, 2021

Our strategy for making islets from ES/iPS cells is now out in Nature Protocols. In this article, Co-first authors Hogrebe, Maxwell, and Augsornworawat illustrate making islets from patient iPSCs (T1D, T2D, MODY, Wolfram Syndrome). We hope that this is a useful resource for other labs. 

Article Link

Congratulations Dr. Leo!

July 27, 2021

Leonardo defended his PhD Thesis on the functional development and maturation of SC-Beta cells. Huge congrats to Dr. Velazco-Cruz!

New Paper on Oxygen Effect on Stem Cell Differentitations

July 12, 2021

Dr. Millman publishes new research article on the effects of physiological oxygen on teratoma formation in Stem cell differentiations

Article Link 

Free access to the article can be found found here:  Link 

Review Paper on Islet Encapsulation Published

June 22, 2021

Dr. Millman publishes a review article on designing encapsulation devices using SC-Islets for T1D treatment. 

Article Link 

New Publication in Science Translational Medicine

June 2, 2021

A team of researchers led by diabetes specialists and biomedical engineers at Washington University School of Medicine in St. Louis and Cornell University has demonstrated that, using a miniscule device, they can implant insulin-secreting cells into diabetic mice. Once implanted, the cells secrete insulin in response to blood sugar, reversing diabetes without requiring drugs to suppress the immune system.

The findings are published June 2 in the journal Science Translational Medicine.

Article Link 

*Portions of this originally published by Washington University School of Medicine

Washu News Link

Cornell News Link

SCIENMAG News Link

Medical News Today Link

Dr. Millman receives tenure!

May 14, 2021

Dr. Jeffrey Millman has been promoted to Associated Professor and granted tenure effective June 1!

Michelle joins Duke University for the MD Program

May 7, 2021

Michelle joined the Millman lab in 2017 and made huge contributions to our work in Diabetes Research. She will now be joining the MD program at Duke University. We bid her farewell and wish her great successes in her future endeavors!

Millman lab members win company pitch competition

April 27, 2021

Millmab Lab members, Leo, Punn, Kristina and Dr. Millman, led Salentra Biosciences is awarded $7500 in funding from the Skandalaris Venture competition.

Link to Article

New review on IPS derived Beta cell applications

April 20, 2021

Dr. Maxwell and Dr. Millman publishes a new review article on the applications of IPS derived Beta cells! 

Link to Article

Marlie joins the Millman Lab!

January 29, 2021

Marlie Maestas joins the Millman Lab as a doctoral student from the DBBS program. Welcome Marlie!

Millman Lab Welcomes new members!

February 14, 2021

The Millman Lab is proud to have additional members join our team. Sarah Gale joins us as our senior lab manager. Diana and Cameron are here to join us as Lab technicians. The two will be conducting research in optimizing and expanding in vitro Islet generation for diabetes cell replacement therapy.

Dr. Millman Received CMBE Award

January 2, 2021

Dr. Jeffrey Millman was named and awarded the 2021 Cellular and Molecular Bioengineering (CMBE) Rising Star by BMES. Congratulations!

Twitter Link 

Congratulations Dr. Maxwell

December 7, 2020

Big congrats to Millman lab Doctoral student, Kristina Maxwell for successfully defending her thesis entitled “Autologous Stem Cell-Derived β Cells for Diabetes Cell Replacement Therapy”. Her work has provided significant contributions to the diabetes cell replacement therapy field. Congratulations Dr. Maxwell!

Millman Lab participates JDRF One Walk

October 31, 2020

Millman Lab team participates this year’s JDRF One Walk fundraising event. The “Beta Squad” team raised funds and enjoyed the St. Louis’s forest park stroll to support research in curing Type I Diabetes. 

Millman Lab at BMES 2020

October 14, 2020

Millman Lab team, Punn Augsornworawat, Kristina Maxwell and Dr. Jeffrey Millman himself will be giving talks at the 2020 BMES Annual meeting. Please check out their talks and feel free to drop by for the live Q&A sessions. 

Kristina Maxwell – Stem Cell Engineering I October 15 3PM-4PM

Jeffrey Millman – Stem Cell Engineering II October 15 9AM-10AM

Punn Augsornworawat – Stem Cell Engineering II October 15 9AM-10AM

Dr. Millman featured on Podcast

September 19, 2020

Dr. Jeffrey Millman spoke at a podcast on the development and advancements of Stem cells for treating type I diabetes. 

Check it out from these links:

Apple Podcasts bit.ly/JBPAPod

Spotify bit.ly/JBPspot

Amazon Music bit.ly/JBPAmazonMusic

Online bit.ly/JuiceboxPod

Leo is awarded NIH F31

August 26, 2020

Congratulations to Millman Lab Doctoral student Leonardo Velazco-Cruz for getting the prestigious NIH F31 Fellowship! His excellent achievements have proven him worthy of this award. The team is proud of his accomplishments. 

August 25, 2020

Millman lab’s recent paper, Single-Cell Transcriptome Profiling Reveals β Cell Maturation in Stem Cell-Derived Islets after Transplantation, is featured on the Cell Reports Journal cover! Check out the released journal issue on the link below. 

Link to website

August 25, 2020

Stem Cell-Derived Islets Now Resemble Human Islets

Researchers at Washington University have been generating insulin-producing islets in the laboratory from human stem cells. This approach promises a virtually unlimited supply of replacement insulin-producing tissues to functionally cure patients with diabetes. However, cell-derived islets are immature compared to islets from the body, lacking the expression of genes associated with maturation.

 

Here, a team of researchers from the laboratory of Dr. Jeffrey Millman at Washington University in St. Louis have discovered that these stem cell-derived islets are capable of maturing after transplantation to resemble real islets more closely from humans. The team, with co-first authors Punn Augsornworawat and Kristina Maxwell, accomplished this feat by developing a new methodology to isolate transplanted cells and performed single-cell RNA sequencing to catalogue these changes in individual cells. 

 

The mice used in the experiments had severe diabetes. After several months, these mice were completely cured of diabetes, with the transplanted stem cell derived islets providing robust insulin release and blood glucose regulation, equivalent to healthy mice. 

 

These long-term improvements in function are associated with increased expression of mature genes, such as MAFA and G6PC2. In addition, the team also identified other mature markers including FAM159B, and MT1X, to robustly confirm maturation and found that secretion of the peptide IAPP to be a detectable biomarker for maturation more robustly.

 

These findings highlight the similarities between lab-grown islets after transplantation and native islets from the body and provides a new technological pipeline allowing for more rigorous study of cellular maturation of differentiated cells from stem cells. The research article was published on August 25, 2020 in the journal of Cell Reports.

This study was supported by the National Institutes of Health (5R01DK114233, T32DK108742, P30CA91842, UL1TR000448), a JDRF Career Development Award (5-CDA-2017-391-A-N), Washington University-Centene Personalized Medicine Initiative, David and Deborah Winston Fellowship in Diabetes Research, and joint funds from Washington University (Departments of Surgery, Medicine, and Pediatrics), Mid-America Transplant Services, and The Foundation for Barnes-Jewish Hospital.

Link to article

New review article on single-cell technologies

August 4, 2020

Punn Augsornworawat and Dr. Millman published a review article on Single-cell RNA sequencing to investigate pancreas development and diabetes. 

Link to article

Leo and Maddy published new article

July 9, 2020

Leonardo Velazco-Cruz and Madeleine Goedegebuure published a review article on β cell development and functional maturation. Congratulations!

Link to article

Millman lab PhD students win travel awards

July 1, 2020

Congratulations to Punn Augsornworawat for winning the MDPI bioengineering travel award and Kristina Maxwell for winning the BME department travel award to attend and present at the BMES conference. We look forward to their talks!

Matt receives Rita Levi-Montalcini Postdoctoral Fellowship

July 1, 2020

Congratulations to our Postdoctoral Fellow, Dr. Matthew Ishahak, for receiving the first Rita Levi-Montalcini Postdoctoral Fellowship in Regenerative Medicine!

Millman lab welcomes new members!

June 15, 2020

We are pleased to welcome Erica Marquez, and the Rita Levi-Montalcini postdoctoral fellow Dr. Matthew Ishahak to join our team. Dr. Ishahak will be using his microfluidic expertise to design devices to model and study the behaviors of stem cell-derived islets. Ms. Marquez will explore strategies to genetically engineer stem cell-derived islets for studying diabetes. We look forward to their future contributions to the diabetes therapy field.

New publication in Cell Reports

May 26, 2020

Congratulations to Leo, Maddy, and the rest of the team for their new publication in Cell Reports! In it, they discovered that the transcription factor SIX2 is essential for the functional maturation of stem cell-derived beta cells. This is important as our team continues to engineer these cells for diabetes cell replacement therapy.

Generation of insulin-secreting β cells in vitro is a promising approach for diabetes cell therapy. Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are differentiated to β cells (SC-β cells) and mature to undergo glucose-stimulated insulin secretion, but molecular regulation of this defining β cell phenotype is unknown. Here, we show that maturation of SC-β cells is regulated by the transcription factor SIX2. Knockdown (KD) or knockout (KO) of SIX2 in SC-β cells drastically limits glucose-stimulated insulin secretion in both static and dynamic assays, along with the upstream processes of cytoplasmic calcium flux and mitochondrial respiration. Furthermore, SIX2 regulates the expression of genes associated with these key β cell processes, and its expression is restricted to endocrine cells. Our results demonstrate that expression of SIX2 influences the generation of human SC-β cells in vitro.

Link to article

Congratulations to Maddy for graduating!

May 22, 2020

Maddy will be moving on to do a PhD at Northwestern. We will miss you!

Diabetes reversed in mice with genetically edited stem cells derived from patients – new publication in Science Translational Medicine

April 22, 2020

Using induced pluripotent stem cells produced from the skin of a patient with a rare, genetic form of insulin-dependent diabetes called Wolfram syndrome, researchers transformed the human stem cells into insulin-producing cells and used the gene-editing tool CRISPR-Cas9 to correct a genetic defect that had caused the syndrome. They then implanted the cells into lab mice and cured the unrelenting diabetes in those mice.

The findings, from researchers at Washington University School of Medicine in St. Louis, suggest the CRISPR-Cas9 technique may hold promise as a treatment for diabetes, particularly the forms caused by a single gene mutation, and it also may be useful one day in some patients with the more common forms of diabetes, such as type 1 and type 2.

The study is published online April 22 in the journal Science Translational Medicine.

Patients with Wolfram syndrome develop diabetes during childhood or adolescence and quickly require insulin-replacement therapy, requiring insulin injections multiple times each day. Most go on to develop problems with vision and balance, as well as other issues, and in many patients, the syndrome contributes to an early death.

“This is the first time CRISPR has been used to fix a patient’s diabetes-causing genetic defect and successfully reverse diabetes,” said co-senior investigator Jeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University. “For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping stone toward applying gene therapy to a broader population of patients with diabetes.”

Wolfram syndrome is caused by mutations to a single gene, providing the researchers an opportunity to determine whether combining stem cell technology with CRISPR to correct the genetic error also might correct the diabetes caused by the mutation.

A few years ago, Millman and his colleagues discovered how to convert human stem cells into pancreatic beta cells. When such cells encounter blood sugar, they secrete insulin. Recently, those same researchers developed a new technique to more efficiently convert human stem cells into beta cells that are considerably better at controlling blood sugar.

In this study, they took the additional steps of deriving these cells from patients and using the CRISPR-Cas9 gene-editing tool on those cells to correct a mutation to the gene that causes Wolfram syndrome (WFS1). Then, the researchers compared the gene-edited cells to insulin-secreting beta cells from the same batch of stem cells that had not undergone editing with CRISPR.

In the test tube and in mice with a severe form of diabetes, the newly grown beta cells that were edited with CRISPR more efficiently secreted insulin in response to glucose. Diabetes disappeared quickly in mice with the CRISPR-edited cells implanted beneath the skin, and the animals’ blood sugar levels remained in normal range for the entire six months they were monitored. Animals receiving unedited beta cells remained diabetic. Their newly implanted beta cells could produce insulin, just not enough to reverse their diabetes.

“We basically were able to use these cells to cure the problem, making normal beta cells by correcting this mutation,” said co-senior investigator Fumihiko Urano, MD, PhD, the Samuel E. Schechter Professor of Medicine and a professor of pathology and immunology. “It’s a proof of concept demonstrating that correcting gene defects that cause or contribute to diabetes — in this case, in the Wolfram syndrome gene — we can make beta cells that more effectively control blood sugar. It’s also possible that by correcting the genetic defects in these cells, we may correct other problems Wolfram syndrome patients experience, such as visual impairment and neurodegeneration.”

In the future, using CRISPR to correct certain mutations in beta cells may help patients whose diabetes is the result of multiple genetic and environmental factors, such as type 1, caused by an autoimmune process that destroys beta cells, and type 2, which is closely linked to obesity and a systemic process called insulin resistance.

“We’re excited about the fact that we were able to combine these two technologies — growing beta cells from induced pluripotent stem cells and using CRISPR to correct genetic defects,” Millman said. “In fact, we found that corrected beta cells were indistinguishable from beta cells made from the stem cells of healthy people without diabetes.”

Moving forward, the process of making beta cells from stem cells should get easier, the researchers said. For example, the scientists have developed less intrusive methods, making induced pluripotent stem cells from blood — and they are working on developing stem cells from urine samples.

“In the future,” Urano said, “we may be able to take a few milliliters of urine from a patient, make stem cells that we then can grow into beta cells, correct mutations in those cells with CRISPR, transplant them back into the patient, and cure their diabetes in our clinic. Genetic testing in patients with diabetes will guide us to identify genes that should be corrected, which will lead to a personalized regenerative gene therapy.”

[portions of this was taken from the WashU press release by Jim Dryden]

Link to article

Link to press release

New patent issued

April 17, 2020

The team just had a new patent issued for our invention of using 3D printing to make a transplantable scaffold for stem cell-derived islets.

Jeffrey R. Millman and Jiwon Song. 3D-printed scaffold device for cell transplantation. 10,597,639. Issued March 24, 2020

Danny awarded fellowship from the NSF

March 29, 2020

Danny has received a NSF Graduate Research Fellowship Program (GRFP) fellowship. This award “recognizes and supports outstanding graduate students in NSF-supported science, technology, engineering, and mathematics disciplines who are pursuing research-based Master’s and doctoral degrees at accredited United States institutions”, according the NSF website.

Danny joins the lab!

March 23, 2020

We are excited to have Danny join the lab as a PhD student in the DBBS program. He will be studying the molecular mechanisms that control cellular fate and health.

New recent fellowships!

February 26, 2020

Congratulations to Dr. Nathaniel Hogrebe and Punn Augsornworawat for receiving the JDRF Advanced Postdoctoral Fellowship and David and Deborah Winston Fellowship in Diabetes Research Award, respectively! 

Diabetes in mice cured rapidly using human stem cell strategy

February 24, 2020

Researchers in the Millman lab have converted human stem cells into insulin-producing cells and demonstrated in mice infused with such cells that blood sugar levels can be controlled and diabetes functionally cured for nine months.

The findings, from researchers at Washington University School of Medicine in St. Louis, are published online Feb. 24 in the journal Nature Biotechnology.

“These mice had very severe diabetes with blood sugar readings of more than 500 milligrams per deciliter of blood — levels that could be fatal for a person — and when we gave the mice the insulin-secreting cells, within two weeks their blood glucose levels had returned to normal and stayed that way for many months,” said principal investigator Jeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University.

Several years ago, the same researchers discovered how to convert human stem cells into pancreatic beta cells that make insulin. When such cells encounter blood sugar, they secrete insulin. Still, previous work has had its limitations and had not effectively controlled diabetes in mice.

Now, the researchers have shown a new technique they developed can more efficiently convert human stem cells into insulin-producing cells that more effectively control blood sugar.

“A common problem when you’re trying to transform a human stem cell into an insulin-producing beta cell — or a neuron or a heart cell —is that you also produce other cells that you don’t want,” Millman said. “In the case of beta cells, we might get other types of pancreas cells or liver cells.”

Off-target pancreas and liver cells don’t hurt anything when implanted into a mouse, but they don’t fight diabetes either.

“The more off-target cells you get, the less therapeutically relevant cells you have,” he said. “You need about a billion beta cells to cure a person of diabetes. But if a quarter of the cells you make are actually liver cells or other pancreas cells, instead of needing a billion cells, you’ll need 1.25 billion cells. It makes curing the disease 25% more difficult.”

Using the new technique, Millman’s team found far fewer off-target cells were produced while the beta cells that were made had improved function. The technique targets the cells’ internal scaffolding, called the cytoskeleton. The cytoskeleton is what gives a cell its shape and allows the cell to interact with its surrounding environment, converting physical cues into biochemical signals.

“It’s a completely different approach, fundamentally different in the way we go about it,” he said. “Previously, we would identify various proteins and factors and sprinkle them on the cells to see what would happen. As we have better understood the signals, we’ve been able to make that process less random.”

Understanding that process has allowed Millman’s team to produce more beta cells. Importantly, the new technique works efficiently across stem cells from multiple different sources, greatly expanding the ability of this technique in the study of disease.

“We were able to make more beta cells, and those cells functioned better in the mice, some of which remained cured for more than a year,” Millman said. “

He explained that there still is much to do before this strategy can be used to treat people with diabetes. They will need to test the cells over longer periods of time in larger animal models and work to automate the process to have any hope of producing beta cells that can help the millions of people who currently require insulin injections to control their diabetes. But the research is continuing.

Portions of this is from the WashU press release linked below:

Press release

Link to article

Celebration dinner!

February 4, 2020

The lab celebrated a couple of paper acceptances, a new fellowship, and several positive reviews on new grants and paper. Great way to start the year off!

Welcome Julia!

January 17, 2020

We welcome Julia into the lab as an undergraduate researcher. She is working with Punn on studying islet heterogeneity.

Welcome Shreya!

January 13, 2020

We welcome Shreya into the lab as an undergraduate researcher. She is working with Kristina on in vitro models of type 2 diabetes.

Congratulations to Michelle for graduating this December

January 8, 2020

Congratulations to Michelle for graduating with her B.S. in Biochemistry from WashU this December!

Dr. Millman awarded a Distinguished Young Alumni Award

January 7, 2020

Dr. Millman was honored with a Distinguished Young Alumni Award from the Chemical and Biomolecular Engineering (CBE) Department at North Carolina State University, the highest award that CBE can bestow on alumni. This honor recognizes the achievements and contributions of alumni to their profession and serves as an inspiration for current and future students.

CBE Distinguished Alumni Award website

Holiday lab lunch!

December 13, 2019

Many reason for us to celebrate this year. New papers, grants, fellowships, award, and graduation! Such a wonderful team!

Labsgiving!

November 25, 2019

The lab celebrated “Labsgiving” this week. Many things to be grateful for!

Madeleine Goedegeburre named a Future Leader in Chemical Engineering

October 23, 2019

Maddy was chosen as a Future Leader in Chemical Engineering from North Carolina State University based on her research in the lab engineering stem cells for the study and treatment of diabetes. Congratulations!

More information

Millman lab presents at this the annual BMES meeting

October 17, 2019

Punn and Maddy presented posters on their work studying differentiation fate and developing screening approaches for diabetes. Also encountered Millman lab alumna Jiwon!

New platform for the assembly of islet organoids from stem cells

August 22, 2019

Co-first authors Punn Augsornworawat and Leonardo Velazco-Cruz published an article entitled “A hydrogel platform for in vitro three dimensional assembly of human stem cell-derived islet cells and endothelial cells” in Acta Biomaterialia. We also congratulate Punn on his first first-author publication! We hope this platform will enable fabrication of advanced regenerative medicine products for diabetes therapy.

View report

Millman lab presents at Oxford and EASD!

August 5, 2019

Jeff and Leo presented at the EASD-Hagedorn Oxford Workshop on the latest protocol for generating functional beta cells for therapy.

Maddy received an Amgen Foundation Scholarship

July 17, 2019

Maddy received an Amgen Scholarship to continue performing research in the Millman lab with stem cells and genetic engineering – congratulations!

Millman lab presents at the annual ISSCR meeting!

June 26, 2019

Kristina presented at the International Society for Stem Cell Research on her work with differentiated patient-derived stem cells

Arvind Srivatsava defends his M.S. thesis

May 8, 2019

Congratulations to Arvind Srivatsava for defending his Biomedical Engineering Master’s Thesis on the microfluidic assessment of stem cell-derived beta cells!

Many Congratulations!

May 7, 2019

Kristina Maxwell received the Greg Sibbel Travel award to present her research at ISSCR and received a leadership award from the BME Department.

Punn Augsornworawat received a BME Department travel award to present his research at BMES.

Maddy Goedegebuure received an Amgen Scholarship to continue performing important work on maturation of stem cell-derived beta cells this summer.

Anu Sharma has been accepted to the Technion-Cornell Master’s Degree in Health Tech program.

Arvind Srivatsava has been accepted to the University of Rochester to pursue at PhD.

Unfortunate for us, this means that this is Anu and Arvind’s last week in the lab. We wish them well in their new degree programs

Acquisition of Dynamic Function in Human Stem Cell-Derived β Cells

January 17, 2019

This is Leo’s first research article! Congratulations to him and the rest of the team!

Press release

Link to article

Methods and compositions for increased safety of stem cell-derived populations

January 15, 2019

Dr. Millman issued a new patent entitled “Methods and compositions for increased safety of stem cell-derived populations,” patent number 10,179,901.