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.
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!
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!
Congratulations Dr. Maxwell
December 7, 2020
Big congrats to Millman lab Doctoral studemt, 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 http://bit.ly/JBPAPod
Amazon Music https://bit.ly/JBPAmazonMusic
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.
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.
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.
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!
Millman lab PhD students win travel awards
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.
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]
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:
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.
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.
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!
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!
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!
Millman lab walks the JDRF walk to support patients!
October 6, 2019
Today we participated in the JDRF One Walk to show our support for patients with diabetes. We raised over $5000 thanks to generous donations!
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.
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!
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
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.
News prior to 2019 archived