Rexxi Prasasya Headshot, Congratulations Graphic

Congratulations Rexxi Prasasya, PhD, K99 Pathway to Independence Award Recipient

Congratulations to Rexxi Prasasya, PhD, who has been awarded a K99 Pathway to Independence Award. Dr. Prasasya, a Research Associate in the Bartolomei Lab, received this award for her project titled “Molecular determinants of sex-specific DNA methylation signature acquisition in the mammalian germline.”

She plans to use this award to continue her research into elucidating how the most sexually dimorphic epigenetic marks, DNA methylation, is established in the germ cells. Aberrant DNA methylation in gametes is associated with idiopathic infertility, poorer outcomes during fertility treatment, and can be deleterious to early embryonic development. Using various mouse genetic models, Dr. Prasasya will be investigating intracellular and extracellular cues that instruct the patterning of DNA methylation in oocytes and sperm.

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.

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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”

New, precise, and efficient DNA sequencing method may lead to easier testing and earlier cancer detection

The study, led by Tong Wang, MD/PhD student in the Kohli Lab, demonstrates a new technique that requires smaller DNA samples for testing and opens up potential new opportunities for next-generation diagnostics. Read the full article at Penn Medicine news or below.


Researchers from the Perelman School of Medicine at the University of Pennsylvania have invented a new way to map specific DNA markings called 5-methylcytosine (5mC) which regulate gene expression and have key roles in health and disease. The innovative technique allows for scientists to profile DNA using very small samples and without damaging the sample which means it can potentially be used in liquid biopsies (testing for cancer markers in the bloodstream) and early cancer detection. Additionally, unlike current methods, it also can clearly identify 5mC without confusing it with other common markings. The new approach, named Direct Methylation Sequencing (DM-Seq), is detailed in a Nature Chemical Biology article today.

Beyond the primary bases of DNA (adenine, cytosine, guanine, and thymine), there is an added layer of information in DNA modifications that control what genes are “on” or “off” in any given cell type. 5mC is considered to be one of the most important of these modifications, as it is the most common type of DNA modification in all mammals and is known for silencing certain genes.

“5mC can act as a fingerprint for cell identity, so it’s important for scientists to have the power to isolate 5mC and only 5mC,” said Rahul Kohli, MD, PhD, an associate professor of Biochemistry and Biophysics at Penn Medicine and a senior author of the study. “DM-Seq uses two enzymes to map 5mC and can be applied to sparse DNA samples which means it could be used, for example, in blood tests that look for DNA released into the blood from tumors or other diseases tissues.” The study was led by Tong Wang, an MD/PhD student in Kohli’s lab.

DNA modifications such as 5mC function as epigenetic (reversible, environmentally-caused) regulators that alter how DNA is read. 5mC involves the attachment of a small cluster of atoms called a methyl group at a particular site on a cytosine, also known as the letter “C” in the four-letter DNA alphabet. The presence of this modification can impede the expression of nearby DNA through direct and indirect mechanisms.

The DNA that is rendered inactive by 5mC includes protein-encoding genes whose activity may not be appropriate in a given cell type at a given stage of life, as well as virus-like elements in DNA that should always be suppressed. Unsurprisingly, the abnormal absence or excess of 5mC can lead to abnormal gene expression, which can drive diseases such as cancers. Certain abnormal patterns of 5mCs are considered signatures of some cancers—which underscores the importance of having an accurate and specific 5mC mapping method.

Methods for mapping 5mC use chemicals or enzymes that react with 5mC and normal unmodified cytosine in different ways, allowing the two to be distinguished. But the traditional method, bisulfite sequencing (BS-Seq), is significantly damaging to DNA, and fails to distinguish between 5mC and another important type of methylation called 5-hydroxymethylcytosine (5hmC). More recently developed methods also have shortcomings including the requirement for relatively large amounts of DNA.

DM-Seq utilizes two enzymes that can modify DNA, a designer DNA methyltransferase and a DNA deaminase, which together can detect 5mC directly and specifically. It also is sensitive enough to be done with nanogram amounts of DNA, which makes it suitable for liquid biopsy applications.

The researchers performed DM-Seq on glioblastoma-type brain tumor samples and demonstrated that, in comparison with traditional BS-Seq, DM-Seq was better able to distinguish 5mC from 5hmC at key sites on the genome where methylation levels can be used to predict patient outcomes.

The researchers also compared DM-Seq to another new, emerging 5mC-sequencing technique called TAPS, which is being explored for potential applications in cancer diagnostics, showing that the latter has a previously undiscovered drawback that reduces its 5mC-detection sensitivity.

“These findings highlight ways in which direct detection of 5mC from DM-Seq, rather than traditional sequencing methods, could advance efforts to use epigenetic sequencing for prognostic purposes in cancer care,” Kohli said.

Along with Kohli and Wang, other Penn authors included Johanna Fowler, Laura Liu, Christian Loo, Meiqi Luo, Emily Schutsky, Kiara Berríos, Jamie DeNizio, Saira Montermoso, Bianca Pingul, MacLean Nasrallah, and Hao Wu.

The research was supported by the National Institutes of Health (R01-HG10646).

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.


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).



Congrats to Liz Heller, Ph.D.for being promoted to Associate Professor of Pharmacology!

We are thrilled to celebrate the promotion of Core Member Liz Heller, Ph.D. to Associate Professor of Pharmacology. Please join us in congratulating Dr. Heller on this great achievement! We are excited to watch as your career continues to grow!

To learn more about Dr. Heller, please visit her lab website:

Kathryn E. Wellen, Ph.D. selected for AACR Award for Outstanding Achievement in Basic Cancer Research

Congratulations to Core Member Kathryn E. Wellen, Ph.D. on being selected for the American Association for Cancer Research Award for Outstanding Achievement in Basic Cancer Research!

This award honors an early-career investigator for meritorious achievements in basic cancer research. A member of the ACC Cancer Therapeutics Research Program, Dr. Wellen is recognized for her research establishing new paradigms in the understanding of cancer cell metabolism. The chemical reactions that change food into energy function very differently in cancer cells compared to healthy cells, and these metabolic processes are a driving force behind cancer growth. Dr. Wellen’s work has shed light on how cancer cell metabolism works at a molecular level, and shown how cellular metabolism is connected to gene regulation. Many of her discoveries have opened new fields of study involving the mechanisms of crosstalk between metabolic pathways, signaling networks, and the epigenome. Building on recent findings, Dr. Wellen’s lab is also investigating how diet and nutrition play impact tumor growth.

Penn Epigenetics Institute Tribute to C. David Allis

C. David Allis
C. David Allis (1951 – 2023)

Dear Epigenetics Institute,

We were all deeply saddened to learn of David Allis’ passing in early January, at far too young an age of 71.  David’s discoveries over nearly 30 years, launching with his groundbreaking 1996 Cell paper reporting the first nuclear histone acetyltransferase, GCN5, had enormous impacts on the fields of histone biology and epigenetics. His ideas and vision extended well beyond these fields, to broadly influence and propel research of nuclear processes in the context of chromatin.  David was elected to scientific academies in the United States, and won numerous prestigious awards, including the Japan Prize, the Life Sciences Breakthrough Prize, and the Albert Lasker Basic Medical Research Award.

I feel personal sadness as my lab group and I were very fortunate to have collaborated with David, and worked in parallel, in the early revelatory years of histone modifications.  I was always amazed by his passion and wide-eyed excitement for new findings that, over the years, led to an ever-expanding reach of histone biology into every aspect of chromatin-based processes.  The field and science as a whole have indeed lost a tremendous spokesman, as his lectures and conference talks were truly inspirational and, without a doubt, recruited many graduate students, postdocs, and medical fellows into the world of epigenetics.

David was an exceptional and universally admired scientist, but he was also an amazing mentor, as is clear from the testimonials below from his postdoctoral trainees Erica Korb, Richard Phillips and Liling Wan, now all, to our great delight, core faculty members of the Epigenetics Institute.

With deep sadness on this occasion,

Shelley Berger, PhD

Erica Korb, PhD

Dave was an incredible scientist, a wonderful mentor, and an incredibly kind and caring person. We’re all devastated by this loss and Dave will be missed by the many, many of us who passed through his lab and were lucky enough to know him and learn from him. One of the things that made him the happiest was seeing his lab members go off to start new labs and train a new generation of scientists. He was particularly thrilled that several of us had the opportunity to come to the Epigenetics Institute to pursue our science. He knew what an amazing place this was and how lucky we were to carry his training to such an incredible environment. Dave was also unfailingly humble and never stopped appreciating the beauty of a simple but elegant experiment. Even in the age of next generation sequencing, Dave’s favorite results were usually in the form of a simple western blot of histone modification. He taught us all that powerful science can come in many forms and we will remember him every time we see a particularly beautiful western blot of histone modifications, that helps to remind us of his favorite saying, ‘Every amino acid matters.’ While we miss him very much, it’s comforting to know that by carrying on his science and training others, we are honoring his memory every day.

Richard Phillips, PhD

Dave was a brilliant scientist. His contributions as a pioneer in chromatin biology are having wide reaching implications in biomedical science and medicine, yet they were borne out of a pure love for discovery and biochemistry which we as trainees witnessed on a regular basis. Dave was one of the most humble individuals you might encounter. Very open minded to new ideas yet deeply rigorous and incisive in his analysis. A unique talent in simplifying complex ideas and making them accessible for other scientists.  But perhaps his most special quality was the care and enthusiasm he had for people. As his mentee you knew he cared about how you were doing outside of the lab. He would cherish news about personal milestones and he loved to decorate his lab with photos lab members shared with him, just one of the many things he did to create a ‘family’ environment. Dave supported, promoted and advised us all so enthusiastically in our scientific careers and he was so excited for his trainees to come to the Epigenetics institute and continue our work in this environment. I will miss Dave sorely but I feel privileged to have been able to learn from such a great man.

Liling Wan, PhD

With the passing of David Allis, the scientific community has lost one of its most inspirational leaders and brilliant minds. Besides his enormous impact on biomedical science and discovery, Dave had influenced many scientists inside (including Erica, Richard, and myself at the Epigenetics Institute) and outside his laboratory through his enthusiasm, kindness, generosity, and support. I have not seen anyone who loved science more than Dave. His genuine interest in science and other people’s work, coupled with his rare gift of simplifying complex ideas and making them accessible to non-experts, inspired and attracted many trainees and collaborators over the years to study chromatin and its role in diverse biological processes. Working in Dave’s lab was a delightful and rewarding experience. He mentored us with relentless positivity and encouragement. He always promoted our careers whenever possible during our training in his lab and continued to do so after we launched our independent careers. His care of people went beyond work. He celebrated trainee’s personal milestones with equal if not more joy as he did for scientific accomplishments. Like many of us in the extended Allis family, I am forever grateful for his mentorship and friendship and aspire to follow his footsteps to bring a positive impact on science and people. His legacy will live on.

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