News

By Erika Brown – November 12, 2024

Breakthrough T1D—a leading organization focused on advancing research and fostering innovation in T1D treatment—paid a visit to the Millman Lab this week. The tour, which was attended by donors and Breakthrough T1D staff, provided an exclusive look at the groundbreaking work being done by researchers in the lab. 

Members of the lab, including Dr. Nathaniel Hogrebe, Ed Sanchez-Castro, and Marlie Maestas presented lab research in a hands-on way to the visitors. The Millman Lab appreciates its close relationship with Breakthrough T1D, and is looking forward to more visits in the future.

By Erika Brown – November 12, 2024

Dr. Matthew Ishahak has been selected by the Biomedical Engineering Society (BMES) and Cellular and Molecular Bioengineering (CMBE) for the 2025 Postdoctoral Researcher Travel Award. The awardees will participate in the 2025 BMES-CMBE conference in January in Carlsbad, CA by giving an oral presentation about their research and will be recognized at the conference gala dinner. 

Congratulations, Matt!

By Erika Brown – November 7, 2024

The Millman Lab participated in this year’s Diabetes Day Symposium hosted by the Diabetes Research Center on November 7, 2024. The DRC hosts this annual symposium each November in recognition of World Diabetes Day, bringing together scientists and trainees to highlight recent advances in diabetes research, foster collaborations, and expand knowledge across institutions. The event features lectures by invited external experts, poster presentations by DRC labs, and one-on-one meetings with researchers. This year’s invited speaker was Dr. Seung Kim, a professor of developmental biology at Stanford. 

Dr. Matt Ishahak and Ed Sanchez-Castro of the Millman Lab presented posters on their research in the lab, with Dr. Ishahak winning the Best Poster award.

By Erika Brown – November 5, 2024

Dr. Jeff Millman and Dr. Nathaniel Hogrebe participated in the 5th Summit on Stem Cell-Derived Islets, hosted by the International Pancreas and Islet Transplant Association (IPITA), the Harvard Stem Cell Institute (HSCI), and Breakthrough T1D (formerly JDRF). The summit took place October 28-29 at Harvard Medical School in Boston.

During the summit, Dr. Hogrebe delivered a presentation titled “Tuning Developmental Signaling During Stem Cell-Derived Islet Differentiation.” Dr. Millman chaired a discussion panel that addressed the manufacturing, scaling, and regulatory challenges for the broad clinical application of stem cell-derived islets. Additionally, he served on the scientific planning committee for the event.

By Erika Brown – November 4, 2024

The Millman Lab welcomes Noyonika Mukherjee to the lab as a postdoctoral researcher. Noyonika, born and raised in Kolkata, West Bengal, India, earned her BS and MS in Microbiology from the University of Calcutta. In 2019, she began her doctoral studies in Biochemistry and Molecular Biology at the Indiana University School of Medicine, Indianapolis, IN, USA, under the guidance of Dr. Andrew T. Templin. Noyonika’s doctoral research was focused on uncovering lesser-known mechanisms of beta-cell cytotoxicity, particularly examining how receptor-interacting protein kinases contribute to islet inflammation and beta-cell death in diabetes pathogenesis. In Fall 2024, Noyonika was awarded the Rita Levi-Montalcini postdoctoral fellowship from Washington University in St. Louis to pursue research in regenerative medicine. She subsequently joined Dr. Jeffrey R. Millman’s lab as a postdoctoral research fellow. Building on her expertise in beta-cell cytotoxic responses, Noyonika aims to integrate the Millman Lab’s advancements in SC-derived beta cell development into her work. Her goal is to create iPSC-derived exocrine and endocrine organoid systems that will deepen our understanding of how environmental factors impact type 1 diabetes. When not in the lab, Noyonika can be found in the kitchen trying out new baking recipes!

By Erika Brown – October 25, 2024

Marlie Maestas was one of two 2024 Winston Fellowship awardees. The David and Deborah Winston Fellowship in Diabetes Research was funded in 2012 to support graduate students conducting diabetes and diabetes-related research in the labs of Diabetes Research Center (DRC) members. The fellowship is now awarded annually from the Division of Endocrinology, Metabolism & Lipid Research to outstanding graduate students who show great promise in diabetes research. It provides monetary support for the recipient(s) research and research-related activities. Congratulations, Marlie!

By Constance Gibbs – October 17, 2024

The Division of Endocrinology, Metabolism & Lipid Research in the Department of Medicine has received a $2.75 million gift through the Anita Palmer Corbin Trust to establish the Anita Palmer Corbin Diabetes Research Endowed Fund. The fund augments a spendable fund to support diabetes research in the division that was previously created by Corbin, who died in 2023.

Diagnosed with Type 1 diabetes at age 10, Corbin learned early in life to meet challenges head-on. She enjoyed a more than 20-year career at St. Louis-based Ralston Purina Co., starting as a senior accountant in 1979. After holding several positions of increasing responsibility, she was named vice president and controller in 1994, becoming the first female officer in the company. Her husband, Daniel E. Corbin Jr., said that while his wife championed many causes throughout her life, diabetes research was among her top priorities.

Annual payout from the endowed fund will be used to support Type 1 diabetes research conducted by Jeffrey Millman, PhD, professor of medicine. Millman successfully converted human stem cells into insulin-producing beta cells that were able to rapidly cure diabetes in mice. He has been honing the process to improve the survival and function of insulin-producing beta cells transplanted into patients.

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.

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!

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.

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.  

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!

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.

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

June 18, 2022

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! 

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!

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

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. 

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

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

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! 

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

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!

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.  

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. 

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

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).

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

July 27, 2021

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

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 

June 22, 2021

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

Article Link 

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

May 14, 2021

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

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!

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

April 20, 2021

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

Link to Article

January 29, 2021

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

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.

January 2, 2021

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

Twitter Link 

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!

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. 

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

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 http://bit.ly/JBPAPod

Spotify http://bit.ly/JBPspot

Amazon Music https://bit.ly/JBPAmazonMusic

Online http://bit.ly/JuiceboxPod

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

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

July 9, 2020

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

Link to article

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!

July 1, 2020

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

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.

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

May 22, 2020

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

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

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

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.

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.

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! 

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

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!

January 17, 2020

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

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.

January 8, 2020

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

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

December 13, 2019

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

November 25, 2019

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

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

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!

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

August 5, 2019

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

July 17, 2019

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

June 26, 2019

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

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!

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

January 17, 2019

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

Press release

Link to article

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.