Golnaz Vahedi appointed Epigenetics Institute co-Director

Golnaz Vahedi, PhD, Appointed co-Director of the Epigenetics Institute

We are pleased to announce that Golnaz Vahedi, PhD, has been appointed co-Director of the Penn Epigenetics Institute. Golnaz will fill the role vacated by Marisa Bartolomei, PhD, upon her appointment as Director of the Center for Women’s Health and Reproductive Medicine at the University of Pennsylvania.

Marisa has long been a leader at Penn in many capacities, including as the co-Director of the Epigenetics Institute, and we are thrilled that she will assume this leadership to build the Center into a great entity.  On the other hand—this news is bittersweet for us, as it means she has left her role as co-Director. We are so grateful to Marisa for all that she’s done for the Epigenetics Institute. Her leadership has been critical in our growth and success over 15 years, and we are very happy she has promised to remain highly involved as a Core Member.

Transitions also provide opportunity to bring new leadership, and we are thrilled that Golnaz has agreed to take on this position. Golnaz is deeply talented, with dazzling computational ability along with exceptional experimental science.  She is well-known internationally for her innovative research to acutely investigate gene and chromatin regulation of T-cell development.  Golnaz has been a constant and passionate contributor to Institute initiatives and events, and in many ways this is a natural step.  In addition, Golnaz is a delightful colleague and wonderfully fun person, very much in the spirit of Penn. We welcome her excitement to join us to continue the positive trajectory of the Institute, and to bring fresh ideas and new perspective. We encourage you to learn more about Golnaz by reading her short bio below.

We hope you all will join us in welcoming Golnaz to her new role, as well as in thanking Marisa for her many years of service.

With sincere appreciation,

Shelley, Gerd, and Colleen

Shelley Berger, Epigenetics Institute Director
Gerd Blobel, Epigenetics Institute co-Director
Colleen Blair, Epigenetics Institute Associate Director

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About Golnaz Vahedi, PhD

Golnaz Vahedi, a native of Iran, is an Associate Professor of Genetics (with tenure) at the Perelman School of Medicine, University of Pennsylvania. Golnaz studied Electrical Engineering at Sharif University of Technology in Iran. Sharif University is known for its large number of elite alumni who join the academic world. Golnaz received her Ph.D. with Drs. Edward Dougherty and Jean-Francois Chamberland in Electrical Engineering at Texas A&M University. She then joined the laboratory of Dr. John O’Shea at the NIH as a postdoctoral fellow to study the epigenomic regulation of T cells. It was in the O’Shea lab that she found studying the epigenome is similar to dissecting electrical circuits. As an independent investigator, she uses systems-based approaches to understand molecular details of gene regulation in the immune system. She is the recipient of a number of awards including the NIH Director’s Award (twice), NIAID K22 Career Transition Award (perfect score), Alfred P. Sloan Fellowship, Chan Zuckerberg Initiative Award, W. W. Smith Charitable Trust, Burroughs Wellcome Fund, and Michael S. Brown New Investigator Research Award. She is currently the Deputy Director of Innovation and Technology, Institute for Immunology & Immune Health. She also serves on the advisory boards of the Cell Press journal Immunity and Science Immunology and is a standing member of GCAT study section.

Mitchell A. Lazar Honored with Prestigious George M. Kober Medal for Pioneering Contributions to Diabetes and Metabolic Research

Congratulations to Mitchell A. Lazar, Core Member of the Epigenetics Institute on receiving the George M. Kober Medal from the Association of American Physicians!

The AAP, an elected society of the nation’s most distinguished physician scientists, was founded in 1885 by seven physicians, including Sir William Osler. The Kober Medal, first presented at the annual meeting in 1925, is the AAP’s highest honor, given in recognition of an AAP member whose lifetime efforts have had an enormous impact on the field of Internal Medicine (or the specific member’s discipline) through the scientific discipline they have brought to the field and the many outstanding scientists that they have trained.

Click here to read the full press release. 

Marisa Bartolomei, PhD, Appointed Director of the Center for Women’s Health and Reproductive Medicine

We are delighted to announce the appointment of Marisa S. Bartolomei, PhD, Perelman Professor of Cell and Developmental Biology, as the new Director of the Center for Women’s Health and Reproductive Medicine (formerly known as the Center for Research on Reproduction and Women’s Health) at the University of Pennsylvania Perelman School of Medicine (PSOM).

Dr. Bartolomei has made instrumental discoveries in advancing epigenetic control of genomic imprinting, which continue to propel the field, in particular for healthy pregnancy and fetal development. Her leadership as co-director of the Epigenetics Institute has been invaluable to our research and training community.  Recently awarded the 2024 March of Dimes Richard B. Johnston, Jr., MD prize, which “honors an outstanding scientist who has advanced the science that underlies our understanding of pregnancy, birth, and prenatal development,” Dr. Bartolomei is a leader in female-based and -biased diseases.

Dr. Bartolomei received her BS from the University of Maryland and PhD from the Johns Hopkins University School of Medicine. She subsequently trained as a postdoctoral fellow with Dr. Shirley Tilghman at Princeton University. In 1993, Dr. Bartolomei was appointed as an Assistant Professor at the University of Pennsylvania, rising to Professor in 2006. She received the 2006 Society for Women‘s Health Research Medtronics Prize for Contributions to Women‘s Health. In 2011, Dr. Bartolomei received the Jane Glick Graduate School Teaching Award for the University of Pennsylvania Perelman School of Medicine, which recognizes excellence in graduate teaching, mentoring, and education.  She was elected as a Fellow of the American Association for the Advancement of Science in 2014. Dr. Bartolomei is the recipient of the 2017 Genetics Society Medal (UK Genetics Society), 2022 Society for the Study of Reproduction Research Award and is a Member of National Academy of Sciences.

In addition to her numerous accolades, Dr. Bartolomei is a revered mentor, one of our strongest advocates for and role model of women in science, and her imprint on our campus is evident through her involved leadership of initiatives such as the PSOM Portrait Review Committee.

Please join us in congratulating Dr. Bartolomei on this new leadership role and thanking her for her continued service and contributions to our scientific community.

Michael Grunstein photo

Penn Epigenetics Institute Mourns the Loss of Michael Grunstein, PhD

The Epigenetics Institute mourns the loss of Michael Grunstein, PhD, whose work is foundational to the study of chromatin and epigenetics. In addition to his groundbreaking scientific discoveries in the 1990’s revealing the central biological role of histones and their acetylation modifications, Michael was also a treasured colleague who challenged those around him in a positive way to advance the field.  My own early research in the transcription and chromatin field was deeply affected by long, memorable, and heated discussions with Michael at many conferences.  Below please find an announcement of Michael’s passing written by Siavash Kurdistani, MD, who was a post-doc and colleague to Michael. Please read Siavash’s wonderful memorial to Michael’s inspiring life and work.

Shelley

Shelley L. Berger, PhD
Director, Penn Epigenetics Institute


Michael Grunstein, PhD
In Memoriam
February 18, 2024

It is with profound sorrow that I share the news of the passing of Michael Grunstein, a distinguished professor, valued colleague and pioneering scientist in the field of chromatin and epigenetics. After a nearly 20-year battle, he succumbed to complications from Parkinson’s disease early this morning, with his family by his side at home. This loss is particularly personal to me as Michael was not only my postdoctoral advisor but also instrumental in helping me establish my independent career at UCLA.

Scientific breakthroughs are narratives of individuals and their journeys. Michael’s story is a prime example of this, illustrating the human elements that drive scientific discovery.

Michael was born in Romania in 1946 into a family of Holocaust survivors. After immigrating to Canada, he built a strong foundation in scientific fundamentals with a B.Sc. in Genetics and Chemistry from McGill University in 1967. He earned his Ph.D. at the University of Edinburgh’s Institute of Animal Genetics, working with Dr. Max Birnstiel in a lab recognized for isolating the first gene (rDNA). Michael then moved to Stanford for postdoctoral research, first with Dr. Larry Kedes in the Department of Medicine where he applied insights from rDNA to investigations of histone mRNA, and later with Dr. David Hogness in the Department of Biochemistry. It was in the Hogness lab that Michael developed colony hybridization, a powerful method that revolutionized gene mapping and chromosome isolation from complex mixtures. The technique, known as a “Grunstein,” was a mainstay of molecular biology research for more than two decades.

Upon joining UCLA in July 1975, Michael chose to study histones, driven by his intrigue with DNA packaging proteins and a deliberate choice to steer clear of what he perceived as the crowded field of transcription regulation research. Initially working with sea urchins, a chance confluence of events, including the destruction of the sea urchin population in the Gulf of California by Hurricane Liza in 1976, prompted him to switch to budding yeast as his model organism. This decision was further catalyzed by the development of a method to transform yeast cells, a breakthrough achieved by Gerald Fink and colleagues in 1978.

Utilizing yeast genetics, the Grunstein lab established that histones were not merely packaging proteins for DNA but contribute to regulation of gene expression. A key breakthrough was the demonstration that histones cooperate with the yeast SIR proteins to establish heterochromatin, a first such model for how specialized domains of chromosomes can be formed. His pioneering discoveries opened a novel field of inquiry and laid the foundation for the study of epigenetics in biology and disease.

Reflecting on Michael’s journey, we can discern the key attributes that lead to scientific breakthroughs. Curiosity led him to find fascination in what many considered mundane—packaging proteins. Creativity guided him to explore questions overlooked by others. Courage was evident in his consequential pivot from sea urchins to a then-emerging model organism—the budding yeast. Willingness to follow nature and experimental results allowed him to perceive that packaging proteins play important roles in gene regulation. Resolve and luck, enabled him to make the best of what was available to him, culminating in seminal contributions to science.

Michael received widespread acclaim for his groundbreaking work, earning him national recognition and his election to the American Academy of Arts and Sciences and the National Academy of Sciences. Among his many awards were the Lasker Basic Medical Research Award, the Albany Prize, the Gruber Genetics Prize and the Massry Prize. He shared these honors with C. David Allis, who credited Michael’s influential work in the 1980s as the inspiration for his own entry into the field of epigenetics.

Michael’s success, like that of many scientists, was made possible by the contributions of a talented group of student and postdoctoral trainees. Additionally, he was fortunate to have the tireless support of his spouse, Dr. Judith (Judy) Grunstein. Judy played a crucial role both within and outside the laboratory setting. She helped Michael establish his laboratory at UCLA and made significant contributions to his research. One notable contribution was an important early paper that characterized the sea urchin histone H4 gene. Later, Judy earned a dentistry degree from UCLA and dedicated over three decades to practicing in the community.

Michael served as Chair of the Department from 2007 to 2010 and retired from UCLA on June 29, 2016.

Beyond his scientific endeavors, Michael had a passionate interest in gardening. He approached gardening not just as a leisure activity but with serious dedication. At its peak, his garden was yielding an impressive 3 tons of avocados annually, in addition to a bountiful variety of other fruits and vegetables.

Michael leaves behind his loving wife Judy, their daughter Davina, their son Jeremy and daughter-in law Elisa, and four grandchildren: Jasper, Rowan, Emilia and Josie. Our thoughts are with the Grunstein family during this immensely difficult time, and we offer them our deepest sympathies and support.

I invite you to listen to Michael’s Lasker speech in which he describes his contributions to science and offers personal reflections on his career:  https://vimeo.com/291819942.

In honor of Professor Grunstein’s inspiring legacy and enduring contributions to the Department,

Siavash

Siavash K. Kurdistani, MD
Professor and Chair
Department of Biological Chemistry
David Geffen School of Medicine at UCLA

Marisa Bartolomei, PhD, Awarded the 2024 March of Dimes Richard B. Johnston, Jr., MD Prize

Congratulations to Epigenetics Institute Co-Director Marisa Bartolomei, PhD on receiving the 2024 March of Dimes Richard B. Johnston, Jr., MD, Prize! Please see the full announcement below, and click here for more information about the Prize. 

March of Dimes, the leading organization fighting for the health of moms and babies, is pleased to announce Marisa Bartolomei, PhD, as the recipient of the 2024 March of Dimes Richard B. Johnston, Jr., MD Prize. This annual award honors an outstanding scientist who has advanced the science that underlies our understanding of pregnancy, birth, and prenatal development. Dr. Bartolomei is a Co-Director of the Epigenetics Institute at the University of Pennsylvania’s Perelman School of Medicine, where she is also the Perelman Professor of Cell and Developmental Biology.

Over her 30-year career, Dr. Bartolomei has made instrumental discoveries on the function and expression of certain genes, called imprinted genes. These genes, whose proper expression is critical for healthy pregnancy and fetal development, can be severely affected by numerous factors, including environmental exposures throughout life and pregnancy.

“Dr. Bartolomei’s astounding body of work on how the abnormal expression of imprinted genes can lead to severe developmental errors and devastating diseases for babies has brought us closer to the development of critical diagnostic and therapeutic interventions,” said Dr. Emre Seli, Chief Scientific Officer at March of Dimes. “I am incredibly excited and honored to present Dr. Bartolomei with this award. She exemplifies the spirit of the prize through her dedication to bridging the divide between science at the bench and medicine at the bedside so the work we do today can improve outcomes for moms and babies tomorrow.”

This award, named in honor of Dr. Johnston, Professor Emeritus of Pediatrics at the University of Colorado and a former Medical Director at March of Dimes, carries a cash award and was created as a tribute to Dr. Jonas Salk, developer of the polio vaccine. It is part of March of Dimes’ research strategy to address the multi-faceted nature of the maternal and child health crisis. To date, six recipients have gone on to win the Nobel Prize in Physiology or Medicine.

Throughout her career, Dr. Bartolomei’s research has addressed the epigenetic mechanisms of genomic imprinting and germline reprogramming as well as the impact of early environmental exposures on epigenetic gene regulation. Imprinted genes, unlike traditional genes, normally express only one copy (one from the mother or one from the father). When things go wrong, as with an epigenetic mutation, these genes will express either both or neither of its copies. This can cause devastating developmental errors during pregnancy that lead to serious disease.

Dr. Bartolomei succeeded in identifying one of the first imprinted genes in 1991. Her later work identified connections between imprinted genes and early developmental disorders like Beckwith-Wiedemann Syndrome, which causes babies to grow too big in the womb and predisposes them to cancer, and Silver-Russell Syndrome, which causes babies to grow too slowly in utero. Her continued work in other related areas has improved our understanding of gene reprogramming, defects in expression, and the impact of environmental exposures, like Bisphenol A (BPA) and phthalates, on healthy development. This work has revealed the critical role of imprinted genes in healthy development, opening new possibilities to prevent and cure disease.

“We are truly just getting started with imprinted genes,” Dr. Bartolomei said. “As the scientific community continues to discover the vital role these genes have in development, others are doing work on new screening tests, therapeutics, and interventions to ensure that imprinted genes are expressed properly, and if they are not, to invent treatments that can be administered to avoid the worst outcomes. And for me, this award is truly exhilarating—when I look at past awardees, some of whom have been important mentors and influenced my career, it’s really special.”

March of Dimes will present the award to Dr. Bartolomei at the 2024 Annual Meeting of the Society for Reproductive Investigation in Vancouver, British Columbia on March 16, 2024.

Dr. Bartolomei received her BS from the University of Maryland and PhD from the Johns Hopkins University School of Medicine. She completed postdoctoral training at Princeton University with Dr. Shirley Tilghman, President Emerita Princeton University. In 1993, Dr. Bartolomei was appointed as Assistant Professor at the University of Pennsylvania, rising to Professor in 2006. She was elected as a Fellow of the American Association for the Advancement of Science in 2014 and is a Member of the National Academy of Sciences.

Congratulations Yanxiang Deng!

Congratulations Yanxiang Deng, 2023 Blavatnik Regional Award Laureate!

Congratulations to Yanxiang Deng, PhD, who has been awarded the 2023 Blavatnik Regional Award for Young Scientists in the Life Science category.

Dr. Deng was recognized for developing a novel microfluidic method for “spatial-omics” to profile expression of RNA, proteins, and epigenetic markers across spatially organized groups of cells in tissues. Deng’s work has allowed us to construct a map of how RNA, proteins, and epigenetic markers are expressed across groups of cells with respect to cells’ relative positions. This work provides critical insight about how cells in different regions change their behavior during processes like development and disease.

The Blavatnik Regional Awards acknowledge and celebrate the excellence of outstanding postdoctoral scientists from institutions in New York, New Jersey, and Connecticut working in the three disciplinary categories of Life Sciences, Physical Sciences & Engineering, and Chemistry.

Click here to learn more about the Blavatnik Awards.

Click here to visit the Deng Lab website.

Award Announcement Graphic

Congratulations to our 2024 Epigenetics Institute At-Large Pilot Grant Awardees!

The Penn Epigenetics Institute is pleased to announce the awardees of the 2024 At-Large Pilot Grants. Since 2013, these pilot grants have supported new research projects across a broad spectrum of topics, from those that involve fundamental studies in epigenetics to more applied or disease-oriented studies that utilize epigenetics as a central component of the research. We were grateful to receive a number of high-quality applications this year, and we are looking forward to seeing the results of the funded projects.

New Awards:

Liling Wan, PhD & Eric Joyce, PhD: “Drugging oncogenic condensates using high-throughput chemical and imagine screens”

Yanxiang Deng, PhD: “Spatial Epigenome Sequencing at Tissue Scale and Cellular Level”

Renewal Awards:

George Burslem, PhD & Andrey Poleshko, PhD: “Unbiased Probe Discovery for Epigenetics Reprogramming”

Erica Korb, PhD & George Burslem, PhD: “Developing tools to examine the role and regulation of histone crotonylation in the brain”

Discovering Cell Identity: $6 Million NIH Grant Funds New Penn Medicine Research to Uncover Cardiac Cell Development

Congratulations to Raj Jain, MD, on this fantastic award! Please read the full news release below or at Penn Medicine News. To learn more about Dr. Jain’s work, please visit his Lab Website.

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Historically, scientists have studied how cells develop and give rise to specialized cells, such as heart, liver, or skin cells, by examining specific proteins. However, it remains unclear how many of these proteins influence the activity of hundreds of genes at the same time to turn one cell type into another cell type. For example, as the heart develops, stem cells and other specialized cells will give rise to heart muscle cells, endothelial cells (lining of blood vessels), smooth muscle cells, and cardiac fibroblasts. But the details of this process remain mysterious.

As a result of a $6 million, seven-year grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH), researchers from the Perelman School of Medicine at the University of Pennsylvania are launching new efforts to uncover how the development and maintenance of heart cells is influenced by DNA. These insights could help drive future research on new therapies for cardiac disease.

Penn Medicine researchers propose that nuclear architecture, which governs the availability of hundreds of genes within a cell, plays a critical role in achieving the proper identity of a cell. Specifically, they plan to study how the packaging and organization of DNA in 3D—meaning understanding how DNA folds and twists in a complex way to fit into the tiny space of a cell nucleus—impacts cell development. The work is supported by their previous research, which shows that nuclear architecture governs cardiac cellular identity during both development and disease.

“This research has the potential to significantly advance our understanding of how cardiac cells arise and keep their identity for a lifetime,” said Principal Investigator Rajan Jain, MD, an assistant professor of  Medicine and Cell and Developmental Biology in the Perelman School of Medicine at the University of Pennsylvania. “By viewing congenital heart disease and other cardiac diseases through the lens of how DNA is organized in the cell, many therapeutic opportunities that have remained untapped may come to light.”

The way the nucleus is organized inside cells plays a crucial role in controlling the genes that determine cell identity. The nucleus acts like the command center of the cell, controlling what genes are accessible or available for use.

The Jain lab’s work suggests that the way the DNA is folded and arranged within the nucleus can determine which genes are accessible and active, influencing the cell’s identity. The way the DNA is folded and organized can be compared to a complex origami structure, where each fold and crease determines the final shape and function. The research aims to unravel the role of genome folding in controlling cell behavior, particularly in heart cells, and to identify key processes involved in this regulation. Researchers will also explore how the spatial positioning of DNA affects gene activity during the development of heart cells. By studying this process, researchers can examine how the identity of heart cells is maintained. This process is important for our overall health; incorrect development of heart cells or altering its identity could contribute to congenital heart disease or cardiomyopathy.

“As I trained it was always assumed that therapies can’t target specific proteins in the nucleus, but that has changed over the last few years,” Jain said. “Leveraging those advancements and past work as an inspiration, I hope this research will eventually allow us to design new medicines that will directly target how DNA is organized.”

This research is supported by the National Heart, Lung, and Blood Institute of the NIH (R35HL166663).

 

 

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