Biochemistry and Molecular Biophysics Graduate Group

BMB Home » Faculty » By Research Interest

pixel Control of Gene Expression and Cellular Programming

Joseph A. Baur, Ph.D.

Molecular mechanisms of aging and caloric restriction

Assistant Professor of Physiology
12-114 Smilow Center for Translational Research
Tel: 215-746-4585 / Fax: 215-898-5408
Lab website

The Baur lab is interested in the basic mechanisms that lead to aging. Age is the most important risk factor for many of the diseases affecting Western society today, including cancer, cardiovascular disease, and neurodegenerative disorders.

Shelley L. Berger, Ph.D.

Role of adaptors in regulation of transcriptional activation in yeast and humans

Daniel S. Och University Professor
Department of Cell & Developmental Biology
9-125 Smilow Center for Translational Research
Tel: 215-746-3106 (office) / Fax: 215-746-8791
Lab website; Epigenetics website

Our research focuses on regulation of the nuclear genome in mammals and model organisms. The long strands of nuclear DNA are associated with packaging proteins, called histones, into a structure known as chromatin, akin to the way thread is organized around a spool. We are particularly interested in changes in this chromatin structure via chemical modification of the histone proteins, and how attachment of certain chemical groups onto the histones leads to altered chromatin function. These targeted structural changes are conceptually like the unraveling of the thread to reach specific, buried sections. We are also fascinated by functional changes in chromatin, caused by these histone modifications, that persist through cell division from one cell into two daughter cells; these persistent, or epigenetic, changes are of particular interest because they are key to normal and abnormal growth: they occur during organismal development into multicellular tissues and organs, and are typically disrupted during abnormal reversal of tissue specialization and growth control as in cancer, as well as during aging of cells and individuals. 

Roberto Bonasio, Ph.D.

Noncoding RNAs in chromatin biology and epigenetics

Assistant Professor of Cell & Developmental Biology
9-136 Smilow Center for Translational Research
Tel: 215-573-2598 / Fax: 215-898-9871
Lab website

My laboratory studies the molecular mechanisms of epigenetic memory, which are key to a number of biological processes, including embryonic development, cancer, stem cell pluripotency, and brain function. Epigenetics allows the inheritance of variation (phenotype) without changes in the DNA sequence (genotype). The fact that pluripotent embryonic stem cells, all sharing the same genome, differentiate into hundreds of cell types implies that information about cellular identity and transcriptional states must be stored somewhere within the cell but not in the primary DNA sequence. It has become apparent that this epigenetic information can be encoded in molecular signatures associated with chromatin, the complex of DNA, RNA, and proteins that packages the genome within the eukaryotic nucleus. These signatures include DNA methylation, histone “marks” and variants, higher-order chromatin structures, and chromatin-associated noncoding RNAs .


Lawrence Brass, M.D., Ph.D.

Molecular basis for intracellular signaling in vascular biology

Professor of Medicine, Pathology & Laboratory Medicine, and Pharmacology
Associate Dean and Director, Combined Degree and Physician Scholar Program School of Medicine
913 Biomedical Research Building II/III
Tel: 215-573-3540 / Fax: 215-573-2189
Combined Degree Program website

Most of the work we are currently doing is devoted to understanding the molecular basis for platelet activation in vivo. Individual projects are looking at the role of heterotrimeric G proteins in initiating platelet activation, low molecular weight GTP-binding proteins in fostering integrin activation, and Eph kinases in maintaining platelet activation. The actual studies are being done in vitro using isolated human platelets and transfected cell systems, and in vivo using genetically engineered mice.


Luca Busino, Ph.D.

Mechanisms of protein ubiquitylation and degradation

Assistant Professor of Cancer Biology
753 Biomedical Research Building II/III
Tel: 215-746-2569
Lab website

My laboratory studies the mechanisms by which the ubiquitin-proteasome system (UPS) controls cell proliferation and how alterations in these processes contribute to tumor initiation and maintenance. Misregulation of protein degradation pathways is often observed in cancer cells. Integrating the study of cellular signals with the molecular mechanisms by which ubiquitin ligases target substrates will advance our knowledge of cancer biology and will provide novel avenues for development of therapeutics.

Areas of interest within the laboratory include, but are not limited to: (i) Signaling Pathways (such as those related to the cell division cycle, DNA damage response, circadian clock, and NFkB signaling) and (ii) Identification of small molecules to target ubiquitin ligases.


Maya Capelson, Ph.D.

Nuclear organization of chromatin and its role in gene regulation and cell differentiation

Assistant Professor of Cell & Developmental Biology
9-101 Smilow Center for Translational Research
Tel: 215-898-0550 (office) / 215-573-7548 (lab)
Lab website

We are interested in how the genome is organized inside the nucleus, and how this organization contributes to functional regulation of gene activity. Spatial organization is mediated by interactions between specific regions of the genome and protein components of nuclear structural scaffolds, such as the nuclear envelope. Entire chromosomes, large chromatin domains and specific genes have been reported to occupy particular places in the nuclear three-dimensional space, in a manner that is correlated with their expression status. Such organization represents a potentially widespread mechanism of gene regulation since specifying the relative position of the DNA template inside the nucleus could influence the probability or kinetics of all possible reactions that are carried out on that template, such as transcription, silencing or replication. Yet many of the basic principles of how particular genomic loci are targeted to and affected by distinct nuclear scaffolds remain obscure. Our goal is to understand how these interactions are determined, how they can change in development or disease states, and how they influence the establishment and inheritance of gene expression patterns.

Sara Cherry, Ph.D.

Genetic and mechanistic studies of viral-host interactions

Associate Professor of Microbiology
304K Lynch Laboratories
433 South University Avenue
Tel: 215-746-2384 /Fax: 215-746-6697
Departmental website

Research in the Cherry lab is aimed at identifying cellular factors that regulate viral pathogenesis, including both those factors hijacked by viruses for replication and those innate anti-viral mechanisms used by the host to combat the invader. To identify these factors we are taking a genetic approach by screening for factors that impact viral replication. To this end, we are using the model genetic organism Drosophila. This allows us to use a wide-variety of techniques to identify these genes including both high-throughput RNA interference screens in cell culture, and forward genetic screens in animals. Moreover, we are also screening for host factors in human cells using high-throughput RNA interference screening technologies. We are using these approaches to study a number of arthropod-borne RNA viruses, including the flavivirus West Nile virus, the alphavirus Sindbis and the bunyavirus Rift Valley Fever virus. These are the three major families of viruses that are important human pathogens transmitted by mosquitoes to humans. By screening in both hosts- insect and human- we hope to gain a more comprehensive understanding of the host factor requirements of these pathogens. We are currently characterizing the roles of candidate genes already uncovered by using molecular biological and cell biological techniques and have discovered factors involved in viral replication and innate immunity. By combining these methodologies, and using a variety of viruses, we hope to gain a comprehensive understanding of the interplay between the host and pathogen in a complex and dynamic setting. Taking advantage of forward genetics and functional genomics in will allow us to use these unbiased and global methodologies to identify many important and novel host factors that modulate virus-host interactions. Moreover, the more viral-host pairs that we study, the better our understanding of pathways and processes essential to pathogens, and the more equipped we will be to develop anti-viral treatments.


Gideon Dreyfuss, Ph.D.

Nuclear transport, hnRNP complexes, RNA-binding proteins, spinal muscular atrophy

Isaac Norris Professor of Biochemistry & Biophysics
Howard Hughes Medical Institute Investigator
328 Clinical Research Building
Tel: 215-898-0398, 215-898-0172 / Fax: 215-573-2000
Lab website / Departmental website / Howard Hughes Medical Institute website

The research efforts of the Dreyfuss laboratory are presently focused on four interrelated topics:

  1. The transport of proteins and RNAs between the nucleus and the cytoplasm
  2. The molecular function of SMN (Survival of Motor Neurons), the protein product of the Spinal Muscular Atrophy (SMA) disease gene
  3. The structure and function of the hnRNP proteins, with particular focus on the role of these proteins in the formation and function of mRNA
  4. Novel phage display methods for identification of interacting proteins.


Benjamin Garcia, Ph.D.

Quantitative proteomics for analysis of chromatin structure and function

Presidental Associate Professor of Biochemistry & Biophysics
9-124 Smilov Center for Translational Research
Tel: 215-573-9423 (office) /215-573-9422 (lab)
Lab website

The Garcia laboratory is focused on developing novel mass spectrometry based proteomic methodologies for quantitatively characterizing changes in protein and proteome expression and post-translational modification state during significant biological events, or in response to external perturbation. Our goal is to utilize large-scale proteomic data to improve our understanding of biological processes at the molecular level. Application of our proteomic technology spans several areas of cellular biology, especially with an interest in epigenetic mechanisms.

Alessandro Gardini, Ph.D.

How global transcription is regulated during cell differentiation and oncogenesis using a variety of genomics and biochemistry approaches.

Wistar Institute Assistant Professor of Biochemistry and Biophysics
The Wistar Institute
3601 Spruce Street
Philadelphia, PA 19104-4265
Tel: 215-898-3785
Lab website

The Gardini lab investigates how global transcription is regulated during cell differentiation and oncogenesis using a variety of genomics and biochemistry approaches. There are three major lines of research in the lab: 1) Role of enhancer and enhancer-derived noncoding RNAs during normal hematopoiesis and leukemia. 2) Role of chromatin remodelers in ovarian cancer. 3) Functional dissection of the Integrator protein complex to characterize its role in a) RNAPII elongation and b) processing of noncoding RNAs.
We integrate genome-wide techniques (such as ChIP-seq, RNA-seq and Global RunOn --GRO-seq-- ) with biochemical purification of transcriptional regulatory complexes to assess their subunit composition and identify novel RNA and protein partners.


Roger Greenberg, M.D., Ph.D.

Basic DNA repair mechanisms that impact cancer etiology and therapy


Associate Professor of Cancer Biology
513 Biomedical Research Building II/III
Office: (215) 746-2738 / Lab: 215-746-7799/ Fax: (215) 573-2486
Lab website

My laboratory uses a multifaceted experimental approach to investigate basic mechanisms of DNA repair that impact cancer etiology and response to therapy. We have a particular interest in understanding chromatin dependent contributions to DNA repair and their impact on the function of breast and ovarian cancer suppressor proteins BRCA1 and BRCA2. In relation to these interests, we have developed novel methodologies to visualize DNA double-strand break responses in real time at the single cell level (Shanbhag et al. Cell 2010; Cho et al. Cell 2014) and used these approaches to define basic features of DNA double-strand break recognition, communication between DNA damage responses and transcription on contiguous stretches of chromatin, and implicate homologous recombination as a key driver of chromatin mobility and alterations to higher order structure.

We provided the first insights into the molecular nature of BRCA1 double-strand break recognition events by reporting that BRCA1 is targeted to lysine63-linked ubiquitin chains at damaged chromatin (Sobhian et al. Science 2007). This occurs through BRCA1 interaction with a 5-membered ubiquitin binding protein complex that selectively interacts with lysine63-linked (K63-Ub) ubiquitin chains. This work implicated nondegradative ubiquitin chains as a recognition signal for the assembly of DNA repair protein complexes at damaged chromatin. Our subsequent studies provided insights into the importance of ubiquitin signaling to BRCA1 dependent DNA repair and tumor suppression (Jiang et al. Genes & Dev 2015; Solyom et al. Science Transl Med 2012; Sawyer et al. Cancer Discov 2015). A second and emerging area of interest in my laboratory is the relationship between homologous recombination and alternative telomere maintenance mechanisms (ALT). We have recently reported a specialized homology searching mechanism is responsible for ALT telomere recombination and developed the tools to visualize this process in real time (Cho et al. Cell 2014). My laboratory will continue this research to define alternative mechanisms of homologous recombination and their functional relationship to telomere maintenance in ALT dependent cancers. Finally, we have devoted considerable effort to understanding the biochemical, structural, and in vivo functions of Zn2+ dependent (JAMM Domain) deubiquitinating enzymes, which play vital roles in the DNA damage response and in inflammatory cytokine signaling.  We have active collaborations that have revealed the structural basis for JAMM domain DUB activation (Zeqiraj et al. Mol Cell 2015) and have developed first in class inhibitors of such enzymes for disease indications that emanate from elevated interferon responses.

Ekaterina L. Grishchuk, Ph.D.

Mechanisms that drive and control chromosome motions in mitosis

Assistant Professor of Physiology
675 Clinical Research Building
Office: (215) 746-8178 / Fax: (215) 573-2273
Lab website

Our goal is to understand the molecular mechanisms that produce force and accuracy for mitotic chromosome motions during cell division. With biophysical, cell biological and computational approaches we study the specialized protein complexes, which function as efficient nanomachines capable of providing durable attachments between chromosomal kinetochores and the assembling and disassembling ends of microtubules. There are no man-made or natural macro-devices that function analogously to these coupling protein complexes, so uncovering the corresponding mechanisms is both challenging and exciting. Current research is focused on kinesin motor CENP-E and the microtubule-binding protein complex Ndc80, which are studied with Total Internal Reflection Fluorescent microscopy and advanced laser trapping techniques. Rigorous understanding of how the kinetochores attach to the dynamic microtubule ends should ultimately assist developing novel and more specific anticancer drugs.

Kushol Gupta, Ph.D.

Structural biology of large macromolecular assemblies that regulate genetic information; X-ray crystallography; small-angle X-ray and neutron scattering.


Research Assistant Professor of Biochemistry and Biophysics
810 Stellar-Chance Building
Office: 267-259-0082
Lab: 215-573-7260

The Structural Biology of Retroviral Integrases. Retroviral integrase (IN) is a dynamic enzyme. While its primary function is to catalyze the incorporation of viral cDNA into the host genome, it also serves other functional roles throughout the viral life cycle. The synaptic complex formed between IN and viral DNA is called the intasome. This complex comprises the core catalytic component of the preintegration complex (PIC): a large viral replication intermediate that directs translocation through the nuclear pore and site-selection for integration into host chromatin. The design of effective pharmacological treatments remains of paramount importance to the treatment of HIV/AIDS. The first HIV IN inhibitors arrived in the clinic in ten years ago and have demonstrated the promise of the intasome as a target. Detailed structural models of full-length IN oligomers in its numerous functional states are essential to new structure-based drug design efforts.

My work on the retroviral integrase (IN) has focused on the understanding of higher-order structure and oligomeric forms of the full-length integrase when bound to host factors and DNA, with the overall goal of determining the molecular details of the larger macromolecular assemblies that underlie the steps of retroviral integration. These studies routinely marry rigorous structural and biophysical methods to approach these fundamental questions, including X-ray crystallography small-angle X-ray and neutron scattering (SAXS/SANS), analytical ultracentrifugation, multi-angle light scattering, and molecular modeling. Most recently these approaches have been brought to bear on an exciting new class of allosteric inhibitors that is able to inhibit IN via selectively modulation of its oligomeric properties.

Xian Hua, M.D., Ph.D.

Signaling and epigenetic regulation of cell homeostasis and tumorigenesis


Professor of Cancer Biology
412 Biomedical Research Building II/III
Office: (215) 746-5565 / Fax: (215) 746-5525
Departmental website
Abramson Cancer Center website

Our research focuses on elucidating the molecular mechanisms whereby menin, a scaffold protein interacting with multiple epigenetic regulators, regulates endocrine cells including pancreatic beta cells, endocrine tumors, and MLL fusion protein-induced leukemia. In particular, we are interested in dissecting the function of menin, which is mutated in an inherited human tumor syndrome, Multiple Endocrine Neoplasia Type 1 (MEN1), in suppressing beta cells and endocrine tumors and in promoting leukemogenesis. We seek to elucidate how Menin suppresses endocrine cells, such as pancreatic beta cells, via regulating histone methylations and expression of pro-proliferative genes. Additionally, we are investigating how menin, which acts as a tumor promoter in MLL fusion protein-induced leukemia, cooperates with wild-type MLL protein to promote leukemia and how the menin and wt MLL axis can be suppressed to improve therapy for this aggressive leukemia. Furthermore, we are exploring how inhibition of menin leads to reversal of the established diabetes in mouse models. Finally, we are investigating the role of post-transcriptional modifications of menin in repressing pancreatic beta cells and in promoting proliferation/survival of MLL fusion protein-induced leukemia.

We are using multiple approaches to carry out the investigation. These include biochemical, molecular and cell biology approaches, animal models, genomics/proteomics/bioinformatics, chemical and pharmacological approaches, and immunological interventions. These comprehensive approaches will provide novel insights into the molecular mechanisms for MEN1 tumorigenesis, regulation of beta cells, and leukemogenesis, paving the way to improve therapy against neuroendocrine tumors, leukemia, and diabetes.

F. Bradley Johnson, M.D., Ph.D.

Telomeres, chromatin, DNA repair and their interface with cell senescence and aging.

Associate Professor of Pathology & Laboratory Medicine
402 Stellar-Chance Labs
Tel:215-573-5037 / Fax: 215-573-6317
ITMAT website

Our lab is interested in the biology of human aging and cancer, and we are focusing particularly on how they are influenced by telomere maintenance and dysfunction. Telomeres are the structures that cap the ends of chromosomes, and this location makes them critical for genome stability as well as particularly susceptible themselves to a variety of insults including oxidative damage, exonucleolytic attack, and inappropriate processing by recombination factors.

Our lab focuses on four areas: 1) investigating mechanisms of telomere maintenance; 2) investigating the biology of G-quadruplexes, which are four-stranded DNA structures formed by G-rich sequences like telomeres; 3) using a mouse model lacking telomerase to learn more about the mechanisms by which telomere dysfunction contributes to age-related pathology; and 4) measuring in human clinical specimens of telomere lengths and capping, telomerase activity, chromatin regulators, and cell senescence.


Rahul M. Kohli, M.D., Ph.D.

Investigating the enzymatic basis for diversity generation in the immune system and pathogens; enzyme mechanisms, chemical biology, protein evolution

Assistant Professor of Medicine, and Biochemistry & Biophysics
502B Johnson Pavilion
Tel: 215-662-2359 / Fax: 215-349-5111
Lab: 509 Johnson Pavilion / Tel: 215-614-0163
Lab website

While we conventionally think of genomic DNA as a simple polymer of A's, C's, G's, and T's, the chemistry of the genome is in fact far more interesting. Our laboratory focuses on the DNA modifying enzymes that provide an added layer of complexity to the genome. These enzymes can be involved in the purposeful introduction of mutations or in the chemical modification of nucleobases, making DNA into a remarkably dynamic entity. Many of these processes are at the heart of the battle between the immune system and pathogens. We utilize a broad array of approaches, which include 1) biochemical characterization of enzyme mechanisms, 2) chemical synthesis of enzyme probes, and 3) biological assays spanning bacteriology, immunology, and virology to study DNA modifying enzymes. Our research program aims to understand, harness and perturb these diversity generating pathways.


Melike Lakadamyali, Ph.D.

Assistant Professor of Physiology
Assistant Professor of Cell and Developmental Biology
764 Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104

My main interest is to study biology at the level of its macromolecular machines and to gain a quantitative biophysical understanding of how these machines drive important cell biological processes. Since new tools enable new biology, I also develop advanced microscopy methods that aim to overcome the limitations of current methods and help us to visualize the macromolecular machineries of the cell in action with high spatiotemporal resolution.

Specifically, I am interested in the molecular machinery involved in two fundamental biological processes: transport machinery that drives intracellular trafficking of vesicles and transcriptional machinery that drives gene expression. At the heart of and common to both biological problems is the interaction of multiple proteins with each other and with other proteins to form functional macromolecular nanoscopic complexes. The spatial and temporal organization of these interactions is tightly regulated and the failure to form these macromolecular complexes in the right place and at the right time can have catastrophic consequences.Studying the spatiotemporal organization and regulation of these macromolecular complexes necessitates non-invasive tools that can visualize them with high spatial and high temporal resolution.

We study cytoskeleton and nuclear organization with super-resolution microscopy.

MItchell A. Lazar, M.D., Ph.D.

Sylvan Eisman Professor of Medicine
Chief, Division of Endocrinology, Diabetes, and Metabolism
Director, Institute for Diabetes, Obesity, and Metabolism a
12-102 Smilow Center for Translational Research
Tel: : 215-898-0198
Lab website

The Lazar laboratory is studying the transcriptional and epigenomic regulation of metabolism. We are particularly focused on the role played by nuclear receptors (NRs). In the absence of ligand, NRs bind to DNA and function as potent transcriptional repressors by recruiting corepressor complexes that include the chromatin modulating enzyme histone deacetylase 3 (HDAC3). We are studying the tissue-specific and physiological roles of the corepressor complexes using by combining genomic, genetic, proteomic, and bioinformatics, and metabolic phenotyping approaches. We are especially interested in the circadian NR Rev-erb alpha, which utilizes the corepressor complex to potently repress transcription. Rev-erb alpha is a key repressive component of the circadian clock that senses heme levels to coordinate metabolism and biological rhythms. We are also studying PPAR gamma, a nuclear receptor that is a master regulator of adipocyte (fat cell) differentiation. Ligands for PPAR gamma have potent antidiabetic activity, and thus PPAR gamma represents a key transcriptional link between obesity and diabetes. The molecular, cellular, and integrative biology of these factors are being studied in mouse and human cell lines as well as in mouse knockin and knockout models. We also have discovered resistin, a novel hormone and target of PPAR gamma that is made and secreted by fat cells in rodents and by macrophages in humans. We have demonstrated that resistin regulates insulin responsiveness, and are now using mice humanized for resistin to test the hypothesis that resistin links metabolism to inflammation in human metabolic diseases.

Nuclear receptors and the transcriptional regulation of metabolism

Mitchell Lewis, D.Phil.

Gene regulation; protein crystallography; structural basis of recognition

John Morgan Professor of Biomedical Research and Education
Department of Biochemistry & Biophysics
813B Stellar-Chance Labs
Tel: 215-898-0711 (lab) 215-898-0949 (office)
Departmental website

The major objective of our research is to understand how proteins respond to metabolites and regulate transcription. Our work has focused on the repressor of bacteriophage lambda and the lac operon of E. coli. For almost half a century, these two systems have served as the paradigm for understanding gene regulation. The primary focus of our lab has been to provide detailed structural information on these two systems.


Shawn C. Little, Ph.D.

Molecular mechanisms of aging and caloric restriction

Shawn C. Little
Assistant Professor
Department of Cell and Developmental Biology
University of Pennsylvania Perelman School of Medicine
Philadelphia, PA
Phone: 215-898-7886

Tissue function and organismal life depend on the ability of cells to generate the correct responses to external cues. We aim to understand how gene expression programs arise in response to patterning signals during embryonic development. We use single molecule imaging, quantitative measurements, biochemistry, and genetics to measure transcription dynamics in individual cells. These measurements reveal how patterning cues modulate transcription and thereby elicit precise gene expression programs at the right time and place in early development.

Kristen W. Lynch, Ph.D.

Transcription bursting dynamics; single molecule measurements; cell fate specification

Professor of Biochemistry & Biophysics, and Genetics
909B Stellar-Chance Labs
Tel: 215-573-7749 (office); 215-573-7756 (lab)
Lynch lab website

Tissue function and organismal life depend on the ability of cells to generate the correct responses to external cues. We aim to understand how gene expression programs arise in response to patterning signals during embryonic development. We use single molecule imaging, quantitative measurements, biochemistry, and genetics to measure transcription dynamics in individual cells. These measurements reveal how patterning cues modulate transcription and thereby elicit precise gene expression programs at the right time and place in early development.


Ronen Marmorstein, Ph.D.

X-ray crystallography, chromatin regulation, tumor suppressors, oncoproteins, kinases, aging, structure-based inhibitor design

Professor of Biochemistry & Biophysics
454 Biomedical Research Building II/III
Tel: 215-898-7740 / Fax: 215-746-5511
Departmental website

The laboratory uses a broad range of molecular, biochemical and biophysical research tools centered on X-ray crystal structure determination to understand the mechanism of macromolecular recognition and post-translational histone and protein modifications in the regulation of gene expression, chromatin and epigenetics. The laboratory is particularly interested in gene regulatory proteins and kinases that are aberrantly regulated in cancer and age-related metabolic disorders such as type II diabetes and obesity, and the use of high-throughput small molecule screening and structure-based design strategies towards the develop protein-specific small-molecule compounds to treat such diseases.


John I Murray, Ph.D.

Embryonic transcriptional regulation; fate specification; cell lineages; C. elegans; microscopy

Assistant Professor of Genetics
437A Clinical Research Building
Tel: 215-746-4387 / Fax: 215-746-6258
Departmental website

The goal of the Murray lab is to understand how genomes encode diverse gene expression patterns and cellular phenotypes. While the genetic code provides a basis for predicting the phenotypic consequences of coding sequence changes, we don’t have an equivalent framework for regulatory sequences. The regulatory code is clearly more complex than the genetic code because it uses combinatorial protein-DNA binding rather than base pairing to achieve specificity. Because there are many regulatory proteins and DNA binding sites, unraveling the importance of each interaction will be challenging.


Hillary C.M. Nelson, Ph.D.

Structural biology; transcription; protein-DNA interactions; heat shock response

Associate Professor of Biochemistry & Biophysics
813A Stellar-Chance Labs
Tel: 215-573-7473
Departmental website


Arjun Raj, Ph.D.

Systems biology; developmental biology; non-coding RNA

Assistant Professor of Bioengineering
Skirkanich Hall, Room 240
Lab website

The Raj lab studies the biology of single cells. The primary motivation for studying biological processes on a cell-by-cell basis is the fact that even genetically identical cells can behave very differently. Many of these differences arise as a consequence of the developmental process, whereby some cells are directed to become, for example, liver cells while others become skin cells. We aim to understand these differences at the molecular level. One of our primary experimental tools is a method we have developed for detecting individual RNA molecules via fluorescence microscopy, yielding very precise, quantitative data about RNA abundance and localization within single cells. One application of this method is the visualization of non-coding RNAs. Recently, researchers have made the exciting discovery that much of the genetic material that was previously thought to be “junk” DNA is actually converted into RNA molecules, and some of these non-coding RNA molecules appear to have direct functional roles in development. We are directly visualizing and localizing these molecules in their cellular context to decipher the mechanisms by which they operate, including potential roles in stem cell differentiation. Another area in which cellular heterogeneity is important is cancer. We are producing RNA expression maps throughout tumor sections at single cell resolution to measure spatial variation in expression during tumor formation and development. We anticipate that such studies will lead to new diagnostic tools as well as a deeper understanding of cancer biology.


James Shorter, Ph.D.

Regulation of beneficial or neuropathogenic prions and amyloids by protein-remodeling factors, molecular chaperones, and small molecules

Associate Professor of Biochemistry & Biophysics
805B Stellar-Chance Labs
Tel: 215-573-4256 (office) / 215-573-4257 (lab)
Lab website / Departmental website

Life demands that proteins fold into elaborate structures to perform the overwhelming majority of biological functions. We investigate how cells achieve such successful protein folding. In particular, we seek to understand how cells prevent, reverse, or even promote the formation of prion and amyloid fibers.


Hongjun Song, Ph.D.

Neurogenesis and Epigenetic/Epitranscriptomic Mechanisms in the Nervous System

Perelman Professor of Neuroscience

Professor of Cell and Developmental Biology

Perelman School of Medicine
University of Pennsylvania
415 Curie Blvd, CRB111B
Philadelphia, PA 19104

Tel: 215-573-2449


Research in Dr. Hongjun Song's laboratory focuses on two core topics: (1) neural stem cell regulation and neurogenesis in the developing and adult mammalian brain and how these processes affect neural function; (2) epigenetic and epitranscriptomic mechanisms and their functions in the mammalian nervous system. The lab is also interested in addressing how dysfunction of these mechanisms may be involved in brain disorders.


Yuanquan Song, Ph.D.

Studying the formation, maintenance and function of neural circuits

Assistant Professor of Pathology and Laboratory Medicine
The Children's Hospital of Philadelphia
3501 Civic Center Boulevard
5064 Colket Translational Research Building
Philadelphia, PA 19104
Office: 215-590-0631
Fax: 215-590-3660
Lab: 267-425-3024
Lab website

The long-term goal of the Song lab is to elucidate the cellular and molecular basis governing the formation, maintenance and function of neural circuits under physiological and pathological conditions, using both Drosophila and mammalian models. With a background in neural development, neural circuits and behavior, fly and mouse genetics, injury and neurodegeneration models, our lab offers a unique skillset and perspective for addressing physiological questions in developmental/functional neurobiology and neurological diseases.

Our lab will be focused on four main themes:
1. Elucidating the mechanisms underlying neural degeneration and regeneration
2. Linking pathways regulating regeneration and neurodegenerative diseases
3. An integrative and comparative strategy to study regeneration and tumorigenesis
4. Drosophila models for neurodevelopmental diseases


David Speicher, Ph.D. 

Cancer proteomics; structure-function of membrane associated proteins: protein chemistry and mass spectrometry

Wistar Institute Professor of Biochemistry & Biophysics
Caspar Wistar Professor in Computational and Systems Biology
151 Wistar Institute
Tel: 215-898-3972
Fax: 215-898-0664
Lab website

Our research group primarily focuses on proteomics of human diseases and structure-function of protein-protein interactions. We are currently pursuing two structure-function projects that primarily utilize biophysical methods, such as isothermal titration calorimetry and sedimentation equilibrium, and mass spectrometry to probe protein structures, protein-protein interactions and function. One project involves the giant membrane skeletal protein spectrin, a human actin crosslinking protein that plays a key role in stabilizing the plasma membrane in most cell types. Current studies focus on the proteotypical spectrin tetramers found in human red blood cells and their role in membrane purturbations caused by hereditary hemolytic anemia mutations. Another project involves structure-function analysis of peroxiredoxin 6, an antioxidant enzyme with glutathione peroxidase activity and phospholipase activity, which plays a critical role in protecting lung and other tissues from damage due to oxidative stress


Gregory D. Van Duyne, Ph.D.

Structural biology; protein-protein interactions; x-ray crystallography

Jacob Gershon-Cohen Professor of Medical Science
Department of Biochemistry & Biophysics
809B Stellar-Chance Labs
Tel: 215-898-3058
Fax: 215-573-4764
Departmental website

We are interested in understanding on a structural and biochemical level how DNA and RNA molecules are maintained and processed by living cells. In addition to the mechanisms and regulation of genome replication and transcription, this includes processes such as DNA repair, site-specific and homologous recombination, transposition, condensation of chromosomes, chromosome pairing and segregation, and RNA trafficking and splicing. Our approach is to establish three-dimensional models of macromolecular assemblies relating to a particular biological question using X-ray diffraction methods and to then develop mechanistic and functional models that can be tested experimentally.


Joshua Wand, Ph.D.

Protein structure and dynamics; molecular recognition and signal transduction; NMR spectroscopy


Benjamin Rush Professor of Biochemistry & Biophysics
905 Stellar-Chance Labs (office)
902-904 Stellar-Chance Labs (main laboratory)
G6 Blockley Hall (NMR laboratory)
Tel. 215-573-7288 (office); 215-573-7289 (main laboratory); 215-573-5969 (NMR laboratory) / Fax: 215-573-7290
Departmental website / Lab website

Dr. Wand's research focuses on exploring the relationships between static structure, structural dynamics and function in a range of protein systems. Current efforts are centered on calmodulin, a main player in calcium-mediated signal transduction, GP130, an somewhat promiscuous interleukin and antigen-antibody complexes. A key concept is the balance between changes in structure (enthalpy) and dynamics (entropy) in the setting of the free energy of association between proteins. They are also interested in similar issues in the context of interactions with small ligands such as drugs. Through these studies a remarkably rich manifold of fast dynamical modes have been revealed and a surprising functional role for them discovered.

The Wand lab is also committed to continuing improvement and development of novel NMR techniques. They have recently focused on high pressure NMR to probe the protein ensemble, sparse sampling methods for rapid and sensitivity-optimized data collection, NMR relaxation methods to measure conformational dynamics throughout the protein and a novel method to approach large soluble, unstable and membrane proteins by solution NMR methods. The latter approach involves the use of reverse micelle encapsulation to provide a protective environment for proteins to allow them to be dissolved in low viscosity fluids such as liquid ethane. The initial idea was to use the low viscosity of ethane to overcome the slow tumbling problem for solution NMR spectroscopy presented by large protein in water. Applications have since been expanded to studies of proteins of marginal stability by employing the confined space of the reverse micelle, suppression of protein aggregation to allow study of intermediates of aggregation such as occur in amyloid formation, and studies of both integral and peripherally anchored membrane proteins.


Kathryn E. Wellen, Ph.D.

Cancer cell metabolism, nutrient sensing


Assistant Professor of Cancer Biology
611 Biomedical Research Building II/III
Tel: 215-746-8599 (office); 215-746-4956 (lab)
Fax: 215-573-6725
Departmental website

Our laboratory is interested in understanding how nutrient metabolism interfaces with signaling and transcriptional networks, with a current focus on metabolic regulation of the epigenome. Diseases such as cancer and diabetes are characterized by significant epigenetic and cell metabolic alterations. Chromatin modifications such as histone acetylation are sensitive to changes in nutrient metabolism, although the contribution of metabolism to epigenetic regulation in normal physiology or in disease states is not known. Current goals of our research include defining the molecular mechanisms that link cellular metabolism to the epigenome and investigating the functional significance of this interaction in cancer and metabolic diseases.


Jeremy E. Wilusz, Ph.D.

Regulation of noncoding RNA biogenesis and function

Assistant Professor of Biochemistry & Biophysics
363 Clinical Research Building
Tel: 215-898-8862
Departmental website

Most of the eukaryotic genome is transcribed, yielding a complex repertoire of RNAs that includes tens of thousands of noncoding RNAs with little or no predicted protein-coding capacity. Among these are well-studied small RNAs, such as microRNAs, as well as many other classes of small and long transcripts whose functions and mechanisms of biogenesis are less clear – but likely no less important. Our goal is to characterize the mechanisms by which these poorly characterized noncoding RNAs are generated, regulated, and function, thereby revealing novel insights into RNA biology and developing new methods to treat diseases. Our current efforts are two-fold. First, we are continuing to characterize the MALAT1 locus, which is over-expressed in many human cancers and produces a long nuclear-retained noncoding RNA. Despite being an RNA polymerase II transcript, the 3’ end of MALAT1 is produced by recognition and cleavage of a tRNA-like structure by RNase P. Mature MALAT1 thus lacks a poly(A) tail, yet is protected from 3’-5’ exonucleases by a highly conserved triple helical structure. Second, we are studying the mechanism by which circular RNAs are produced and function. These circular transcripts are generated from protein-coding genes via an unusual pre-mRNA splicing reaction, yet it is largely unclear why the splicing machinery selects certain regions of the genome (and not others) to circularize.


John H. Wolfe, V.M.D., Ph.D.

Glycoproteins; lysosomal enzymes; storage diseases; gene transfer into brain

Professor of Pathology & Medical Genetics
Director of Walter Flato Goodman Center for Comparative Medical Genetics,
School of Veterinary Medicine and Stokes Institute, Children's Hospital of Philadelphia
502G Abramson Building (CHOP)
Tel: 215-590-7028 (office) / 215-590-7029 (lab) / Fax: 215-590-3779
Lab website

Animal homologs of human genetic diseases are used as test systems for gene transfer by viral vectors or stem cell therapies focused on the central nervous system. The include ex vivo gene transfer using genetically modified neural stem cells and direct injection of herpes, adeno-associated and lentivirus vectors. The studies involve transport within neural systems of proteins and/or vectors, properties of transduction for different cell types and various subregions of the brain, modification of therapeutic proteins for improved bioavailability, gene and protein array analysis of mechanisms of pathology and as biomarkers for pathology and response to therapies, stem cell development including diseased human iPSCs, and MRI and PET strategies for non-invasive monitoring of therapies.


Kenneth S. Zaret, Ph.D.

Investigating transcription factor interactions with chromatin

Joseph Leidy Professor, Department of Cell and Developmental Biology
9-131 Smilow Center for Translational Research
502G Abramson Building (CHOP)
Tel: 215-573-5813 (office) / 215-573-5844 (lab) / Fax: 215-898-9871
Lab website

The goal of Dr. Zaret's laboratory is to understand how genes are activated and different cell types are specified in embryonic development. These processes involve regulatory mechanisms that are used later in life to maintain human health, to respond to tissue damage, and during the initiation of cancers and other human diseases. The laboratory has two general approaches. First, we investigate the molecular signaling pathways that commit an undifferentiated embryonic cell, the endoderm, to a particular cell type fate, using the specification of liver and pancreas cells as a model. In the past year, we developed a fate map of the foregut endoderm in the mouse embryo, we discovered how a gene regulatory protein controls morphogenesis so that endoderm cells are properly positioned to receive organ-inductive signals, and we found distinct roles for blood vessel cells in promoting the growth of liver and pancreatic tissues at the earliest stages of organ development. The second approach of the laboratory is to investigate ways that gene regulatory proteins control the packaging of DNA in the cell nucleus, to control gene activity. Biochemical studies revealed that the regulatory protein FoxA possesses a protein segment that interacts with chromosome structural proteins, or histones, and is necessary for exposing genes sequences in chromosomes that are otherwise hidden by the histone proteins. Understanding how regulatory proteins and cell signals control gene activity and cell type decisions in development will help guide future efforts to control the differentiation and function of cells at will.


Zhaolan (Joe) Zhou, Ph.D.

Epigenetic control of genome function in brain development and disease

Assistant Professor of Genetics
452A Clinical Research Building
Tel: 215-746-5025 / Fax: 215-573-7760
Lab website

A fundamental question in biomedical research is how the brain executes genetic programs while maintaining the ability to adapt to the environment. The underlying molecular mechanisms are not well understood, but epigenetic regulation, mediated by DNA methylation and chromatin organization, provides an intricate platform bridging
genetics and the environment, and allows for the integration of intrinsic and environmental signals into the genome and subsequent translation of the genome into stable yet adaptive functions in the brain. While we can now profile genome-wide DNA methylation at single-base resolution, how the methylome is established and maintained,
and how the cells interpret the methylome to affect gene expression and chromatin structure remain poorly understood. Moreover, recent studies have challenged the stability of the methylome in postmitotic neurons and have coupled changes in DNA methylation at specific loci to adaptive behaviors. We are interested in understanding
how DNA methylation is coded and decoded genome-wide but with locus-specificity in neurons. Given the high abundance of hydroxymethylcytosine in the brain, we are also interested in understanding the role of the methylome in establishing and maintaining neuronal identity and the molecular mechanisms by which the methylome modulates genome function in the brain.