Affiliated Labs

Michael C. Abt, Ph.D.

Assistant Professor of Microbiology (Penn Medicine)
Michael C. Abt, Ph.D.'s Website

Our research focuses on the pathogenesis of and host response to Clostridioides difficile, a bacterium that infects the large intestine following perturbation of the intestinal microbiota. C. difficile represents one of the most urgent public health threats in the United States with high recurrence rates following antibiotic treatment, which highlights the need to identify alternative strategies to control this disease.

Mohamad-Gabriel Alameh, Ph.D.

Assistant Professor, Department of Pathology and Laboratory Medicine

Our lab is focused on understanding the structure-activity relationships (SARs) of nucleic acid delivery systems and their associated adjuvant properties to improve the safety, reactogenicity, and potency of emerging mRNA therapeutics. 

We aim to apply these insights in developing mRNA-based vaccines against bacterial pathogens, especially those with urgent threat designations across regions of the world including low- and middle-income countries (LMICs). Our approach involves engineering novel delivery systems and their payloads for cell and tissue-specific treatments.

Juan Alvarez, Ph.D.

Assistant Professor of Cell and Developmental Biology (Penn Medicine)
Juan Alvarez, Ph.D.'s Website

We study how circadian rhythms shape cell development and maturation, using human stem cell- derived organoids as research models and as therapies for human diseases.

We embrace diversity, equity, and inclusion. We strive to deliberately counteract unconscious bias and historical disenfranchisement by nurturing the diversity of our members, providing equitable access no matter race, ethnicity, gender, age, sexual orientation, neurocognitive and physical abilities, or religion, and by fostering opportunities for people underrepresented in science.

Ravi K Amaravadi, MD

Professor of Medicine (Hematology-Oncology) (Hospital of the University of Pennsylvania)
Ravi K Amaravadi, MD's Website

The Amaravadi Lab focuses on the role of autophagy in cancer therapy. Cancer therapy has made major strides in the past 20 years, but eventually most cancers have the ability to survive the stress of cancer therapy and recur, leading to suffering and death. We and others have demonstrated that autophagy, the process by which organelles such as mitochondria and proteins are internally digested and recycled, promotes cancer cell survival in advanced cancers, and is a potentially key resistance mechanism that cancers use to survive cancer therapy.  Our lab collaborates closely with other basic scientists, clinical researchers, biotechnology and pharmaceutical companies so that we can test our hypotheses in cell lines, 3D culture, mouse models, and patients. We conduct basic laboratory research to understand fundamental aspects of autophagy in cancer biology, but we also have a translational focus. We are actively conducting innovative clinical trials intended to modulate autophagy to enhance effectiveness of existing therapies. Our funding comes largely from the National Cancer Institute, focused pharmaceutical collaborations, and private donations from patients and fundraising programs.

Raiees Andrabi. Ph.D.

Division of Infectious Diseases (Penn Medicine)

A major focus in Andrabi laboratory is to utilize in vitro directed evolution platform combined with structure-guided design approaches to develop vaccine immunogens against complex pathogens such as HIV, Influenza virus, Arenaviruses and Coronaviruses. The other major area of research in the laboratory is to understand the immunological basis of B cell affinity maturation pathways to complex antigen surfaces, both in vaccination and in infection and to utilize this information for designing more effective vaccines. The overall goal is to design vaccine immunogens and immunization strategies that can induce protective broadly neutralizing antibody responses against complex pathogens through vaccination in humans.

Montserrat C. Anguera, Ph.D.

Associate Professor, Department of Biomedical Sciences (University of Pennsylvania School of Veterinary Medicine)
Montserrat C. Anguera, Ph.D.'s Website

Our laboratory investigates X-chromosome Inactivation, and how this epigenetic process contributes to female-biased autoimmunity.

We are investigating how female lymphocytes maintain X-chromosome Inactivation, which is an epigenetic process responsible for equalizing gene expression between sexes.  X-chromosome Inactivation silences one X-chromosome in female cells, and this process is initiated and maintained by the long noncoding RNA Xist.

Yoseph Barash, Ph.D.

Associate Professor of Genetics (Penn Medicine)
Yoseph Barash, Ph.D.'s Website

We focus on understanding RNA biogensis, its regulation, and its role in human disease and in phenotipic diversity. Much of our work involves modeling alternative splicing regulation and non-coding regulatory elements in the 5’/3′ UTR. The lab works in three main directions that pose computational, engineering, and experimental challenges:

• Deriving new mechanistic insights into RNA biogenesis.

• Applying our predictive algorithms for RNA processing to the study of human disease and phenotipic diversity.

• Developing software tools that allow the greater scientific community to employ our algorithms.

Nancy Bonini, Ph.D.

Florence R.C. Murray Professor of Biology (Penn Arts & Sciences)
Nancy Bonini, Ph.D.'s Website

The Bonini lab is focused on studies of genes involved in neurodegenerative disease and the stress response. Recent work has included studies of epitranscriptomic modifications associated with the brain upon acute stress, with disease and with age, the most prominent risk factor of neurodegenerative disease.  The lab uses the model organism Drosophila to study the brain and these diseases.

Rick Bushman, Ph.D.

William Maul Measey Professor in Microbiology (Penn Medicine)
Rick Bushman, Ph.D.'s Website

Our goal is to carry out research on interactions between humans and their microbes that yields the maximum positive effect on human welfare. Often this involves development and implementation of new technology for basic research and biotechnology. One research focus involves studies of the human microbiome, the gigantic community of microbes that live associated with every human. Other research centers on specific viruses, such as SARS-CoV-2 and HIV, and the full populations of viruses in humans—the virome. A third related area involves methods for understanding and improving approaches to human gene therapy, including integration by viral vectors.

Our laboratory supports a core facility that provides genomic analysis for human gene therapy, with particular focus on the consequences of gene modification for the human genome: Viral/ Molecular High Density Sequencing Core.

Brian Capell, Ph.D.

Assistant Professor of Dermatology and Genetics (UPenn)
Brian Capell, Ph.D.'s Website

The Capell Lab seeks to answer fundamental questions regarding how epigenetic processes (histone, RNA, DNA) play a role in epithelial diseases such as skin cancer. Our RNA-related research focuses on epitranscriptomics and RNA-modifications (specifically m6A), and how they interface with chromatin and gene regulatory elements during development, homeostasis, and cancer.

Keywords: Epigenetics, Cancer Biology, Skin and Epithelial Biology

Dawn Carone

Associate Professor, Biology (Swarthmore College)
Dawn Carone's Website

The Carone lab investigates noncoding RNA from repetitive regions of the human genome and their misregulation in disease.

Sara Cherry, Ph.D.

John W. Eckman Professor of Medical Science (Penn Medicine)
Sara Cherry, Ph.D.'s Website

The Cherry Lab is interested in the interface between viruses and hosts. The Lab uses chemical and genetic screening technologies to perform a wide array of cell-based screens in human and insect cells studying emerging RNA viruses. The laboratory is interested in emerging and globally important arthropod-borne viruses including the three major families that infect humans: the flaviviruses, alphaviruses and bunyaviruses. We are interested in how these viruses are able to hijack cellular factors from insects to humans for their replication using only a small number of proteins. And how these viruses evade immunity is poorly understood. More recently the lab has expanded their studies to the emerging coronaviruses which have more species and cell type specific tropism. The lab explores how the innate immune system, the first line of defense, can recognize and respond to these invaders. Since much of the recognition of these invaders is at the level of nucleic acid recognition, and these are all RNA viruses, we have been exploring the role of RNA binding proteins and the RNA decay machinery in innate antiviral defense against these viruses. We are systematically exploring antiviral innate signaling activities in diverse cell types targeted by these viruses. For example, in the respiratory epithelium in the case of SARS-CoV-2 and neurons in the case of encephalitic arthropod-borne viruses. Moreover, arthropod-borne viruses infect the vector insect enterically, we use Drosophila to model these intestinal infections to explore the role of microbiota and innate defenses in the gut in the response to enteric arboviral infections.

Peter Choi, Ph.D.

Assistant Professor of Pathology and Laboratory Medicine (Penn Medicine)
Peter Choi, Ph.D.'s Website

Our laboratory is interested in how alterations in RNA splicing drive cancer and expose potential therapeutic vulnerabilities.

Keywords: RNA-binding proteins, functional genomics, cancer genetics

Crystal Conn, Ph.D.

Assistant Professor of Radiation Oncology (Penn Medicine)
Crystal Conn, Ph.D.'s Website

We focus on the dynamic RNA regulation for adaptive responses, with a specific interest in understanding how aggressive cancer cells rewire their translational machinery to select distinct RNAs for protein expression.

Keywords:  Cancer, Protein synthesis, RNA modifications

Beverly Davidson, Ph.D.

Director, Raymond G. Perelman Center for Cellular and Molecular Therapeutics (CHOP)
Beverly Davidson, Ph.D.'s Website

Our lab is focused on genetic diseases that affect the brain. We study the mechanisms by which mutant gene products contribute to disease, and why certain brain regions are more susceptible. The team employs advanced molecular methods, sequencing and imaging modalities in animal models. The lab is also engaged in the development of next generation therapeutics for inherited disorders, including the engineering of novel gene therapy vector capsids and cargo to approach tissue and cell type specific treatments.

James Eberwine Ph. D.

Elmer Holmes Bobst Professor of Pharmacology (Penn Medicine)

Overall, my lab has been interested in the role of variability within cells as a driver of biology and to address the omics of this, we developed the nucleic acid amplification procedures that enabled the field of single cell transcriptomics.  Our current work focuses on understanding the subcellular organelles that interact to give rise to the emergent properties of cells. Much of this relies upon RNA biology and as such we have been developing methodologies, that permit quantitative analysis and functionalization of multi-RNAs and their modifications in individual organelles.

Keywords: single cell, single organelle, RNA biologies

Harvey Friedman, M.D.

Professor of Medicine (Infectious Diseases) (Penn Medicine)

Harvey Friedman’s laboratory is developing vaccines for preventing and treating genital herpes. The vaccine design is based on basic discoveries made by the lab about immune evasion strategies of the virus. We showed that HSV-1 and HSV-2 glycoprotein gC bind complement component C3b, a critical complement protein in the complement cascade. We determined that gC inhibits complement activation, rendering the complement system ineffective against the virus. HSV mutant viruses unable to bind C3b are highly susceptible to complement-mediated neutralization or lysis. In vivo studies in guinea pigs and mice demonstrated that these mutant viruses are 50- to 100-fold less virulent than wild-type virus. Studies in C3-deficient animals demonstrated that virulence of gC mutant viruses returned to wild-type levels, supporting an important role for gC in immune evasion.

The lab also determined that HSV-1 and HSV-2 evade antibody attack. Glycoprotein gE binds the Fc domain of IgG. When the Fab domain of an antibody molecule binds to an HSV antigen, the Fc end of the same antibody molecule binds to gE, blocking activities mediated by the Fc domain, such as complement activation and antibody-dependent cellular cytotoxicity. The impact is that gE reduces the effectiveness of antibodies in host defense. HSV-1 and HSV-2 gE mutant viruses are more susceptible to antibody and complement attack than wild-type virus. These studies establish an important role for gC- and gE-mediated immune evasion in HSV-1 and HSV-2 pathogenesis.

Brian Gregory, Ph.D.

Professor of Biology (Penn Arts & Sciences)
Brian Gregory, Ph.D.'s Website

The Gregory lab studies the roles of RNA structure, RNA-binding protein interaction, and covalent nucleotide modifications on post-transcriptional regulation to affect organismal phenotypes in the context of stress responses relevant to global climate change.

Kushol Gupta, Ph.D.

Research Assistant Professor of Biochemistry and Biophysics (Penn Medicine)
Kushol Gupta, Ph.D.'s Website

Kushol Gupta is a structural biologist interested in the structure and function of protein-nucleic acid interactions, including RNA interactions with HIV Integrase and Phenylalanine Hydroxylase. Kushol also directs the Johnson Foundation Structural Biology and Biophysics core, which features technologies such as SEC-MALS, DLS, AUC, and SAXS – all methods ideally suited for the characterization of LNPs and nucleoprotein assemblies.

Keywords: structural biology, small-angle scattering, solution biophysics

Beatrice H. Hahn, M.D.

Professor of Medicine (Hematology-Oncology) (Penn Medicine)

My laboratory has a long-standing interest in elucidating the origins and evolution of human and simian immunodeficiency viruses and in studying HIV/SIV gene function and disease mechanisms from an evolutionary perspective. My group was the first to describe the extensive in vivo genetic variability of HIV-1 (Hahn et al., Science, 1986) and to discover that recombination between highly divergent viruses represents a major driving force of HIV/SIV diversification (Robertson et al., Nature, 1995). We also developed methods for the non-invasive detection of SIV in wild-living apes, which led to the identification of the chimpanzee and gorilla reservoirs of pandemic and non-pandemic HIV-1 (Gao et al., Nature, 1999; Keele et al., Science, 2006; d’Arc et al., PNAS, 2015). This work has recently come full circle with the discovery that a highly divergent SIVcpz Env may be suitable to immunofocus HIV-1 bNab responses to the Env trimer apex (Barbian et al., mBio, 2015; Andrabi et al., Cell Rep, 2019).

Kathryn Hamilton, Ph.D.

Assistant Professor of Pediatrics (Gastroenterology, Hepatology and Nutrition) (Penn Medicine)
Kathryn Hamilton, Ph.D.'s Website

The Hamilton lab studies how RNA binding proteins regulate epithelial cell fate and function in the gastrointestinal tract.

Keywords: RNA binding proteins, epithelial stem cells, IGF2BP1, METTL3

Elizabeth A Heller, PhD

Associate Professor of Pharmacology (Penn Medicine)
Elizabeth A Heller, PhD's Website

The Heller Lab studies the gene regulatory mechanisms that underlie psychiatric disease. To approach this problem, we apply preclinical mouse paradigms of drug addiction and depression to define functionally relevant histone modifications and transcription factors. Because the syndromes of addiction and depression persist long after cessation of the insult, chromatin remodeling is an attractive mechanism for such long-lasting effects and presents an intriguing target for therapeutic intervention. We use high-throughput sequencing and bioinformatic approaches, including machine learning, to identify genes at which drug- or stress-regulation of the epigenome correlates with changes in gene expression. Using novel epigenetic editing tools, we then target individual modifications and examine their causal relevance to transcription and behavior. This ‘bottom-up’ approach allows direct elucidation of the causal relevance of epigenetic remodeling in the brain.

Chris Hunter, Ph.D.

Mindy Halikman Heyer Distinguished Professor of Pathobiology (University of Pennsylvania School of Veterinary Medicine)
Chris Hunter, Ph.D.'s Website

Research Areas: Infectious Disease, Toxoplasma gondii, Zoonotic diseases, Host-pathogen interactions, Immunology, Parasites, Parasitology, Transgenic parasites, Inflammatory responses

Taku Kambayashi, MD, PhD

Professor of Pathology and Laboratory Medicine (Penn Medicine)
Taku Kambayashi, MD, PhD's Website

Our lab focuses on signal transduction pathways employed by cells involved in fundamental immunological processes and in immune-related disorders. We aim to understand the mechanistic underpinnings of these processes so that we can identify novel targets for therapeutic intervention or for diagnostic/prognostic value.

Research interests: Regulation of T cell responses; Signal transduction; regulatory T cell expansion and homeostasis; Regulation of skin barrier function

Peter Klein, Ph.D.

Professor of Medicine (Hematology-Oncology) (Penn Medicine)

The Klein lab is studying the role of GSK-3 in splicing factor function in normal hematopoiesis, MDS, and leukemia. We are currently focusing on how pathogenic splicing factor mutations alter mitochondrial function and how this can be targeted therapeutically.

Keywords: splicing, GSK-3, Wnt, leukemia, mitophagy

Lan Lin, Ph.D.

Assistant Professor of Pathology and Laboratory Medicine (Penn Medicine)
Lan Lin, Ph.D.'s Website

The Lin Lab studies RNA modifications (“epitranscriptomics”) in human health and disease. Post-transcriptional RNA processing and modifications are key mechanisms for gene regulation and functional diversity in eukaryotic cells. We develop and apply high-throughput sequencing strategies and transcriptome engineering technologies to study the regulation and function of RNA modifications, including alternative splicing, A-to-I RNA editing, and m6A RNA methylation. We also develop and apply omics technologies for RNA-based diagnostics and therapeutics.

Kathy Fange Liu, Ph.D.

Assistant Professor of Biochemistry and Biophysics (Penn Medicine)
Kathy Fange Liu, Ph.D.'s Website

The Liu Lab is affiliated with the Department of Biochemistry and Biophysics at the University of Pennsylvania Perelman School of Medicine. We utilized a battery of biochemical, cellular, and high-throughput sequencing approaches to study the function of RNA modifying enzymes and sex chromosome-encoded protein homologs in human physiology and disease.

Kristen Lynch, Ph.D.

Benjamin Rush Professor of Biochemistry (Penn Medicine)
Kristen Lynch, Ph.D.'s Website

The Lynch lab studies the mechanisms and consequences of regulated RNA processing, such as alternative splicing and polyadenylation, that occurs in human cells during an immune response

Keywords: RNA binding proteins, Alternative Splicing, Alternative Polyadenylation

Michael J. Mitchell, Ph.D.

Associate Professor Bioengineering (Penn Engineering)
Michael J. Mitchell, Ph.D.'s Website

The Mitchell Lab is based in the Department of Bioengineering at the University of Pennsylvania. Our research lies at the interface of biomaterials science, drug delivery, and cellular and molecular bioengineering to fundamentally understand and therapeutically target biological barriers. We apply our research findings and the technologies developed to a range of human health applications, including cancer metastasis, immunotherapy, genome editing, cardiovascular disease, and regenerative medicine. Current research projects include: synthesis of novel biomaterials and nanoparticles for the delivery of nucleic acids (siRNA, miRNA, mRNA, CRISPR-Cas9) for cancer therapy; engineering of immune cells for immunotherapy and vaccines; investigating the influence of biomaterial chemical structure on in vivo transport to target cells and tissues using high-throughput screening platforms; and novel drug delivery technologies for tissue engineering and regenerative medicine.

Andrew J. Modzelewski, Ph.D

Assistant Professor of Molecular Biology, Biomedical Sciences (UPenn School of Veterinary Medicine)
Andrew J. Modzelewski, Ph.D's Website

The Modzelewski lab (The ModzLab) studies early mammalian embryonic development with a specific focus on the role of retrotransposon reactivation, a well-known but poorly understood phenomenon that occurs in all mammalian preimplantation embryos. We discovered that retrotransposon reactivation is not only intentional in the embryo, but it is essential. Our goals is to apply what we learn from normal retrotransposon biology in the embryo to the unintentional retrotransposon reactivation that frequently occurs during epigenetic breakdown associated with aging, autoimmunity,  neurodegeneration and cancer.

Keywords: Retrotransposons, noncoding RNA, development

Zissimos Mourelatos, M.D.

Professor of Pathology and Laboratory Medicine (Penn Medicine)

Fundamental and applied studies on small regulatory RNPs, RNAi, mRNA translation and decay.

Vladimir R. Muzykantov, Ph.D.

Founders Professor in Nanoparticle Research (Penn Medicine)

Our main goal is to dissect the basic signaling mechanisms leading to malignant transformation and the metastatic dissemination of cancer cells. By identifying and characterizing key cellular elements contributing to cancer progression, our research aims to unfold novel targets for the therapeutics of cancer and other diseases.

We are committed to the training of postdoctoral fellows, graduate students and undergrads in a world-renowned institution. Our mission is to provide trainees with outstanding research skills and contribute to their development as successful scientists in a highly collaborative environment. We welcome trainees with a passion for learning and the desire to executing challenging research projects.

Norbert Pardi, Ph.D.

Assistant Professor of Microbiology (Penn Medicine)
Norbert Pardi, Ph.D.'s Website

mRNA-based platform development

In vitro transcribed (IVT) mRNA emerged as a groundbreaking new therapeutic modality that proved its viability as a vaccine platform during the COVID-19 pandemic. Besides vaccination, IVT mRNA can potentially be used for a wide range of clinical applications such as protein replacement, antibody therapy, and genome editing. Our group is interested in further improving the mRNA platform by examining the contribution of mRNA’s structural elements, chemistry, and composition as well as exploring ways to alter its stability, translatability and inflammatory capacity. We believe that a better understanding of these important features of mRNA biology and production will allow for a more precise and optimized mRNA design for various applications.

mRNA vaccine development for infectious diseases

The lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccine platform – being utilized in the mRNA-1273 and BNT162b2 vaccines against SARS-CoV-2 – is saving lives every day in the COVID-19 pandemic. The flexibility of mRNA vaccine design and its highly scalable manufacturing enable the rapid development of modified vaccines adjusted to new variants of SARS-CoV-2 and the production of hundreds of millions of vaccine doses in just a few months. These beneficial features of the nucleoside-modified mRNA-LNP technology are critical for successfully battling quickly mutating pathogens and dealing with pandemic outbreaks where rapid development of production of novel vaccines are key for success.

​Our lab quickly reacted to the SARS-CoV-2 outbreak by designing, producing and testing novel SARS-CoV-2 mRNA vaccines similar to mRNA-1273 and BNT162b2. As the SARS-CoV-2 pandemic is the third coronavirus outbreak in less than 20 years, we have no doubts that coronaviruses will be responsible for more epidemics and pandemics in the near future. We are committed to contributing to global pandemic preparedness, a pro-active approach that aims at designing, producing, and testing new vaccines against pathogens with high pandemic potential. As part of a team of investigators at various institutions, we are developing mRNA-based pancoronavirus vaccines that can elicit broad protection against multiple coronaviruses and help to significantly decrease the negative impact (morbidity, mortality, economic loss) of future coronavirus outbreaks.

Hamideh Parhiz, Ph.D.

Assistant Professor, Systems Pharmacology and Translational Therapeutics

“The Parhiz Lab is located in the Department of Systems Pharmacology and Translational Therapeutics at Penn Medicine, University of Pennsylvania. Our lab develops novel nucleic acid delivery systems, including a new generation of targeted lipid nanoparticle (tLNP), for in vivo cellular reprogramming. We leverage these systems for mRNA-based therapeutics in a variety of non-vaccine applications such as inherited diseases, acquired or congenital hematopoietic conditions, cancers, fibrosis, and acute inflammatory conditions. We also investigate the mechanisms underlying the enhancement of delivery systems such as the ones related to more favorable pharmacokinetic profile, to apply those principles in designing more effective gene and mRNA therapeutics.  Currently, the targeted LNP-mRNA platform we design serves as the foundation for ongoing academic programs and industrial product developments.”

Research keywords: Nucleic acid-based therapeutics, Nano-engineering, Targeted delivery of nanomedicine, mRNA therapeutics

Alexander Price, Ph.D.

Assistant Professor (Wistar Institute)
Alexander Price, Ph.D.'s Website

The Price Lab studies how DNA viruses take over and subvert host cell biology, with a particular focus on how viruses steal cellular RNA processing machinery to make viral RNA. While viruses have evolved to be masters of molecular mimicry, viruses are constrained by a hard limit on maximum genome size. Any viral process that deviates from standard cell biology allows a host cell to sense infection, and transcription of these small genomes can lead to aberrant nucleic acids that can be sensed by the innate immune system. Beyond virology, our research reveals how transcriptional processes affect innate immunity and inflammation, with broad implications for the progression of autoimmune diseases and cancers where RNA biogenesis has become dysregulated.

Keywords:

Viral infection, RNA Transcription, RNA Processing, Nucleic Acid Sensing, Innate Immunity

Stefano B Rivella, Ph.D.

Professor of Pediatrics (Hematology) (CHOP)
Stefano B Rivella, Ph.D.'s Website

The Rivella laboratory is located at the Children’s Hospital of Philadelphia, which is the nation’s first hospital devoted exclusively to the care of children. Since 1855, CHOP has been the birthplace for many dramatic firsts in pediatric medicine. The Hospital has fostered medical discoveries and innovations that have improved pediatric healthcare and saved countless children’s lives. Our laboratory is located in the Leonard and Madlyn Abramson Pediatric Research Center and in the Colket Translational Research Building.

Andrew Santiago-Frangos, Ph.D.

M. Jane Williams and Valerie Vargo Presidential Assistant Professor of Biology
Andrew Santiago-Frangos, Ph.D.'s Website

The Santiago-Frangos lab integrates bioinformatics, biochemistry, and structural biology to address complex biological and biotechnological questions. Our mission is to determine how: i) bacterial and archaeal CRISPR adaptive immune systems make DNA-based memories of past phage infections, and ii) how CRISPR-generated nucleotide messengers signal an immune response. We’ll repurpose these mechanistic insights to develop medical and biotech applications.

Keywords: CRISPR-Cas, Integration, Transposition, Reverse Transcription, Signaling Cascade, Diagnostics

George M. Shaw, M.D., Ph.D.

Professor of Medicine (Hematology-Oncology) (Penn Medicine)

My laboratory has a longstanding interest in the molecular biology and immunopathogenesis of human immunodeficiency virus (HIV-1) and hepatitis C virus (HCV).

Previous highlights of this work include the first molecular clones of HIV-1 (Shaw et al., Science 1984); discovery of the quasispecies nature of HIV-1 in vivo (Saag et al., Nature 1988); discovery of the dynamic and persistent nature of viral replication in vivo (Clark et al., N Engl J Med 1991; Piatak et al., Science 1993; Wei et al., Nature 1995); mechanisms of virus persistence in the face of evolving cellular and humoral immune responses (Borrow et al., Nature Medicine 1997; Wei et al., Nature 2003); and molecular identification and biological characterization of transmitted/founder HIV-1 genomes and their progeny (Keele et al., Proc Natl Acad Sci USA 2008; Salazar et al., J Exp Med 2009; Li et al., PLoS Pathogens 2010).

We extended the work to simian immunodeficiency virus (SIV) infection of rhesus macaque monkeys (Keele et al., J Exp Med 2009) and HCV infection of humans (Li et al., PLos Pathogens 2012; Li et al., J Virol 2015; Ke et al., PNAS 2018).

Most recently, we have developed novel strategies for constructing simian-human immunodeficiency virus (SHIV) chimeras that replicate efficiently in rhesus macaques (Li et al., PNAS 2016; Li et al., J Virol 2021) and induce broadly neutralizing antibodies (Roark et al., Science 2021).

James Shorter, M.A., Ph.D.

Professor of Biochemistry and Biophysics (Penn Medicine)
James Shorter, M.A., Ph.D.'s Website

In the Shorter lab, we examine how sequence, structure, post-translational modifications, protein disaggregases, and short RNAs can affect the self-assembly of RNA-binding proteins (RBPs) with prion-like domains (PrLDs), such as FUS and TDP-43. We seek to leverage our emerging understanding of FUS and TDP-43 liquid-liquid phase separation (LLPS) and aggregation, to design new therapies for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43 encephalopathy (LATE).

Keywords: TDP-43/FUS, ALS/FTD, RNA therapeutics

Hongjun Song, Ph.D.

Perelman Professor of Neuroscience (Penn Medicine)
Hongjun Song, Ph.D.'s Website

We are interested in understanding the roles and mechanisms of RNA modifications (epitranscriptomics) in regulating the mammalian nervous system using mouse and human brain organoid experimental model systems.

Andrei Thomas-Tikhoneko, Ph.D.

Professor of Pathology and Laboratory Medicine (Penn Medicine)
Andrei Thomas-Tikhoneko, Ph.D.'s Website

Our current research focuses on the role of non-coding RNAs (including microRNAs) and mRNA splicing in cancer pathogenesis and therapeutic resistance.

Bin Tian, Ph.D.

Wistar Institute Professor of Biochemistry and Biophysics (Wistar)
Bin Tian, Ph.D.'s Website

Tian is a molecular systems biologist whose research is focused on understanding how gene expression is regulated at the RNA level. His lab was among the first to discover the widespread nature of alternative polyadenylation (APA) using bioinformatic and genomic approaches. They have also revealed multiple molecular mechanisms that regulate APA and cellular functions of APA isoforms in a number of biological systems.

Blanton Tolbert, Ph.D.

Jacob Gershon Cohen Professor of Biochemistry and Biophysics, RNA Structural Biology Lead

Tolbert is a Professor of Biochemistry and Biophysics at University of Pennsylvania. The research in the Tolbert group focuses on the biochemical mechanisms by which RNA viruses replicate within the cellular environment. His group leverages their fundamental understanding of the molecular biology of these viruses to identify novel targets for therapeutic intervention. The team has collaborated with colleagues to develop compounds with the potential to delay or halt the replication of SARS-CoV-2 and EV-A71.

Tolbert earned a BS in chemistry at University of South Carolina and a PhD in biophysics and structural biology at University of Rochester. He was an HHMI postdoctoral fellow at University of Maryland, Baltimore County, with HHMI Investigator Michael Summers. In 2016, Tolbert received the inaugural Morton L. Mandel Award for Excellence in Research and Service from the CWRU chemistry department. In 2023, he was recognized by the International Society for Antiviral Research with the Diversity in Science and Excellence Award.

Susan Weiss, Ph.D.

Professor of Microbiology (Penn Medicine)

My lab focuses on Coronavirus replication and pathogenesis. Most relevant to the institute we study viral enzymes that cleave RNA (CoV Endoribonulease U and oligonucelotides (CoV 2’,5’ phosphodiesterases) as well as host ribonuclease L, that restricts viral replication. We also study viral double stranded RNA binding proteins.

Drew Weissman, M.D., Ph.D.

Roberts Family Professor in Vaccine Research (Penn Medicine)
Drew Weissman, M.D., Ph.D.'s Website

The Weissman lab studies nucleoside-modified mRNA and lipid nanoparticle (LNP) therapeutics. Our findings of the safety and efficacy of nucleoside-modified mRNA have moved this technology to the forefront of new therapeutics. The lab’s technology is used in the first 2 FDA approved COVID-19 vaccines. The lab broadly studies 2 directions of mRNA research: 1) vaccines and 2) mRNA protein therapeutics, such as monoclonal antibody delivery and gene editing. While interested in developing new therapeutics, the lab’s main interest is basic science research. Any therapeutic approach being studied always involves extensive basic science investigation to understand mechanisms.

The lab has an extensive portfolio of vaccine studies, including viral, bacterial, parasitic, oncologic, and allergic diseases. A main interest in the lab is the development of vaccines for difficult diseases where previous vaccine strategies have failed, such as genital herpes, HIV, HCV, malaria, and tuberculosis. We work with experts in the fields for each vaccine that allows the use of optimal animal model systems and assays to measure effectiveness. New vaccines that will be effective against drifted and pandemic influenza strains, paninfluenza, and all coronaviruses capable of crossing over from bats, pancoronavirus, are being developed. In addition, novel vaccines that will be effective at treating common food and environmental allergies are being evaluated.

Protein therapeutics is the fastest growing element of the pharmaceutical industry. We believe nucleoside-modified mRNA offers a superior approach to deliver such proteins, as the host is the factory that makes the proteins. Numerous nucleoside-modified mRNAs encoding therapeutic proteins, including monoclonal antibodies, acute care therapies, and genetically deficient proteins are ongoing. Nucleoside-modified mRNA offers many advantages for gene therapy, including transient and controllable activity. The main impediment to in vivo gene therapy is the need to specifically target the therapy to the cells of interest. We have developed new technology that specifically delivers LNPs to: lungs, heart, brain, CD4+ cells, all T cells, and bone marrow stem cells. This targeting allows the delivery of gene editing systems to the specific cells and organs that require gene manipulation with simple intravenous injections of targeted mRNA-LNPs.

The goals of the Weissman lab are multifold. We seek to develop new nucleoside-modified mRNA-LNP platforms for vaccines, protein therapeutics, and gene therapy. This includes new platforms for vaccines and their application to many different types of diseases. To change and advance protein therapeutics by more safely and efficiently delivering proteins and extending this to therapies that require intracellular protein activity. To develop gene therapies using newly developed methods to alter the genome delivered by nucleoside-modified mRNA and delivered with targeting LNPs, thus allowing simple intravenous administration to achieve in vivo gene modification. Finally, we extensively investigate the basic science and mechanisms for our new therapies, which allows careful and directed optimization to improve them.

Yi Xing Ph.D.

Professor of Pathology and Laboratory Medicine (CHOP)
Yi Xing Ph.D.'s Website

Our lab is broadly interested in the computational biology and genomics of RNA processing and regulation, as well as their applications to human genetics, precision medicine, and cancer immunotherapy.

Joseph Zackular

Assistant Professor of Pathology and Laboratory Medicine

Joseph Zackular, PhD is an Assistant Professor in the Department of Pathology and Laboratory Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia. The Zackular laboratory is focused on understanding how interactions between the host, gut microbiota, and pathogenic microbes impact human health and disease.  The labs efforts primarily center on the nosocomial pathogen, Clostridioides difficile, which is an urgent public health threat.  The Zackular lab is interested in understanding how the gut microbiota shapes C. difficile fitness and virulence, and the team is developing novel mRNA vaccines for the prevention of C. difficile infection. Dr. Zackular is co-director of the Center for Microbial Medicine at the Children’s Hospital of Philadelphia, which is dedicated to finding cures and improving pediatric health through the lens of the microbiome.

David Zappulla, Ph.D.

Associate Professor, Molecular Biology (Lehigh University)
David Zappulla, Ph.D.'s Website

The Zappulla research group studies the telomerase RNP enzyme, telomere length maintenance, lncRNAs, and senescence triggered by telomere erosion and aging.

Lijun Zhou, Ph.D.

Assistant Professor of Biochemistry and Biophysics (Penn Medicine)

We are interested in structures and functions of non-natural nucleic acids, including self-assembly, 3D structure, and effects on protein translation.

Keywords: Non-natural nucleic acid, in vitro selection, nanostructure