| Faculty | Research projects/interest | |
|---|---|---|
| Katherine Aird, PhD | kaa140@pitt.edu | The lab focuses on bidirectional control of metabolism and the cell cycle with interests in cancer, senescence, and aging. We use cell culture models, in vivo cancer/aging models, CRISPR screens, high throughput data, and metabolomics to mechanistically explore these concepts and translate our findings by identifying targetable pathways. Current rotation projects include nutrient exchange between senescent cells and cancer/immune cells and metabolic changes driven by tumor suppressors/oncogenes. Other projects that fall under the umbrella of metabolism with be considered. Projects are tailored to the unique interests of each lab member. |
| Imad Al Ghouleh, PhD | ima6@pitt.edu | As a cardiovascular biology lab our primary focus is to study the molecular mechanisms underlying vascular endothelial dysfunction in pulmonary hypertension (PH) as well as the mechanisms of right heart fibrosis, dysfunction and failure. Current projects are: 1-) Studying the role of endothelial-to-mesenchymal transition of pulmonary vascular endothelial cells in pulmonary hypertension; 2-) studying the role of microbiome-derived metabolites in pulmonary vascular remodeling during pulmonary hypertension |
| Gavin E. Arteel, PhD | gearteel@pitt.edu | Our group is investigating the magnitude and impact of the changes to the hepatic matrisome in the context of the development and recovery from liver disease. As the main detoxifying organ in the body, the liver has tremendous ability to heal and regenerate from injury. The regenerative response in the liver can be perturbed and impacts recovery from injury or damage. The extracellular matrix (ECM) consists of a diverse range of components that work bi-directionally with surrounding cells to create a dynamic microenvironment that regulates cell signaling, recruitment, and tissue function. The basic definition of the ECM comprises fibrillar proteins (e.g., collagens, glycoproteins and proteoglycans). More recently, groups have extended the definition to include ECM affiliated proteins, regulator/modifier proteins and secreted factors (i.e., the ; 'matrisome'). Quantitative and qualitative changes to the ECM structure and superstructure can impact overall health of the organ and organism. Remodeling of the hepatic ECM/matrisome in response to injury is well understood in some contexts. For example, changes to the ECM associated with fibrosis are considered almost synonymous with hepatic ECM changes. Proteomic-based studies in other organs haves demonstrated that the matrisome responses dynamically in composition after insult well before fibrotic changes to the organ. These changes to the ECM may not alter overall ECM architecture and are therefore histologically undetectable. Nevertheless, these changes have potential to alter hepatic phenotype and function. These acute responses can be viewed as an arm of the wound healing response and facilitate recovery from damage, which resolves once the damage is repaired. However, under conditions of chronic injury, these changes likely contribute to activation of a significant remodeling response that leads to scar formation (i.e., fibrosis). It is our goal to better understand this process, as well as to develop minimally-invasive biomarkers to predict interindividual risk. |
| Christopher Bakkenist, PhD | cjb38@pitt.edu | T cell cycles – A project to study how DNA replication and transcription are coordinated in T cells is available. Since T cells divide extremely rapidly and have a short G1 phase, the majority of transcription has to occur with DNA replication in S phase. A mechanism that ensures DNA and RNA polymerases travel through genes in the same direction is essential to prevent DNA-RNA polymerase collisions. A mechanism that allows the synthesis of a single, long transcript through multiple T cell cycles is also essential as long genes cannot be transcribed within a single T cell cycle. |
| Juliane Beier, PhD | JIBEIER@pitt.edu | Dr. Beier’s research focuses on interactions of environmental chemical exposures and lifestyles that increase risk of chronic liver disease and which may be preventable. Obesity and its associated liver disease (i.e., NAFLD/NASH) are epidemic in the US population; indeed, it is estimated that up to 30% of US adults have underlying liver disease, most likely predominantly due to obesity. The impact of this new status quo in the risk of liver injury caused by environmental exposures is understudied. Importantly, such an interaction would imply that risk may be underestimated at this time. Vinyl chloride (VC) is a known human hepatotoxicant that causes a spectrum of both benign and malignant diseases, including hepatocellular carcinoma (HCC), hemangiosarcoma and toxicant associated steatohepatitis (TASH). However, these direct effects of VC exposure require high occupational exposures and have limited relevance with existing VC safety regulations. The impact of low environmental exposures, in contrast to high occupational exposures to VC, is unknown. Importantly, the effect of low exposure must consider aspects that may modify hepatotoxicity. In this context, the impact of underlying disorders (i.e., obesity) or lifestyle choices (i.e., diet) that may modify risk is critical. The Beier lab has demonstrated that low doses of VC that are not overtly hepatotoxic, may serve as a contributing factor in the development and progression of liver disease and cancer and is now working on the underlying mechanisms. Current available projects include: • What are the mechanisms of the interaction between exposure and liver disease? Elucidating and analyzing mitochondrial dysfunction, organelle miscommunication and epigentetic/epitranscriptomic changes. • What are the mechanisms by which low level VC can promote tumor formation and enhance carcinogenesis? • Can we prevent/predict/treat this interaction? This would include pharmacologic or genetic interventions in cell culture and animal models. |
| Robert Binder, PhD | rjb42@pitt.edu | Projects will contribute to major areas of ongoing investigations in the lab; (1) immune responses generated to nascent tumors (2) structural interactions of CD91 with its ligands for generating immune responses, (3) role of heat shock proteins in immune responses |
| Timothy Burns,MD, PhD | burnstf@upmc.edu | My research and clinical interests revolve around the development of targeted therapies for KRAS-mutant NSCLC as well as novel strategies to overcome resistance to targeted therapies for EGFR-mutant and MET-altered NSCLC. My three main research themes are 1) novel pre-clinical target validation and drug development (TWIST1 in oncogene driven NSCLC and TKI resistance); and 2) elucidating mechanisms of resistance for targeted inhibitors to develop rationale therapeutic combinations that can be tested in the clinic (Hsp90, ERK1/2 inhibitors and 4th generation EGFR TKIs) and 3) development of targeted therapy approaches for the treatment of brain metastases. The first line of research in my laboratory focuses on the role of the EMT transcription factor TWIST1 in oncogene-driven NSCLC. We have demonstrated the TWIST1 is essential for lung tumorigenesis for KRAS mutant, EGFR mutant and MET mutant/amplified NSCLC and TWIST1 overexpression leads to resistance to EGFR and MET TKIs. We are examining the mechanism(s) through which this occurs and developing therapeutic combinations to overcome this resistance. Importantly, we have developed a novel TWIST1 inhibitor which serves a tool compound for our therapeutic studies and serves as the basis for our current drug screening efforts to develop a clinical TWIST1 inhibitor. The second line of research in my lab focuses on studying the mechanisms of resistance to targeted agents currently in phase 1 and 2 trials to develop rationale therapeutic combinations in the clinic. This is typified by our previous work with Hsp90 inhibitors and ongoing work on ERK inhibitors and a novel 4th generation EGFR TKI. Finally, my lab is interested in lung cancer brain metastases, and we are exploring whether targeting the HGF-MET-TWIST1 pathway can be an effective strategy for preventing or treating lung brain metastases. In additional to these preclinical studies, we are using both radiogenomic and cell free DNA approaches to predict molecular phenotypes of brain metastases to identify patients with brain metastases that can benefit from MET targeted therapy in the clinic. |
| Wei Du, MD, PhD | duw@upmc.edu | Bone marrow failure, leukemia, DNA damage and immune response, Hematopoietic stem cell-bone marrow niche interactio |
| Aditi U. Gurkar, PhD | agurkar1@pitt.edu | Lab rotation projects include: 1. The role of cellular senescence in cardiac disease 2. Metabolic-epigenetic axis in aging |
| Tija Jacob, PhD | tcj11@pitt.edu | 1. Identification of mechanisms underlying tolerance to benzodiazepines (BZ), a critical clinical sedative-hypnotic drug class. These drugs potentiate GABA type A receptors, the main fast inhibitory neurotransmitter receptor in the central nervous system, and are used for treatment of insomnia, anxiety, and seizures disorders. We are applying proteomic, biochemical, novel optical methods and electrophysiological approaches to identify synaptic neuroplasticity mechanisms induced by BZ treatment. GABA type A receptors (GABAARs) regulate and reduce excitation in the adult brain and also govern development of early brain circuitry. Dysfunction of α5 subunit containing GABAAR contributes to neurodevelopmental disorders including autism spectrum disorders. Although little is known about α5 GABAARs, drugs targeting this receptor’s activity are being tested in human clinical trials. This project focuses on identifying core α5 regulatory mechanisms and employing genetic and pharmacological manipulation to determine how α5 GABAARs sculpt early brain circuit architecture in the rodent nervous system. |
| Yu Jiang, PhD | yuj5@pitt.edu | 1. P53 in androgen dependence of prostate cancer cells. This project explores the role of p53 tumor suppressor in androgen receptor expression and androgen independence of prostate cancer cells. Skills will be learned include RNA-seq, co-Immunoprecipitation and fluorescent imaging. 2. Metabolism in quiescent cancer cells. This project compares energetic metabolism between dividing and non-dividing cancer cells. Skills will be learned include energetic metabolism analysis using Seahorse XF Analyzer and confocal imaging. |
| Michael Jurczak, PhD | jurczakm@pitt.edu | Dr. Jurczak’s lab is primarily interested in the relationship between nutrient excess, mitochondrial overload and the pathogenesis of metabolic diseases, such as fatty liver, insulin resistance and type 2 diabetes. |
| Lee- Oesterreich | leeav@upmc.edu oesterreichs@upmc.edu | The Lee-Oesterreich team uses state-of-the-art technology to understand treatment resistance and progression in breast cancer. Focus areas are endocrine resistance, lobular breast cancer, metastases and precision medicine. For details, please see https://leeoesterreich.org/ |
| Edwin Levitan, PhD | elevitan@pitt.edu | Neuropeptide release and rhythmic behaviors: We use cutting edge optical methods in vivo with genetics and behavior experiments to study the mechanism of neuropeptide release and the impact of neuropeptides on circadian rhythms and sleep. Based on novel Fluorogen Activating Proteins (FAPs), we are determining how fusion pore dynamics, activity and signaling gate the release of small neuropeptides and larger neurotrophins at native synapses. Furthermore, in the brain we are mapping differentially timed neuropeptide release by the clock circuit and determining how separately triggered release at two neuronal compartments (synapses and neuronal cell bodies) controls behavior. |
| Yael Nechemia-Arbely, PhD | arbelyy@upmc.edu | Optimizing DiMelo-seq for various applications - Examining the relationship of CENP-A/C/T centromere proteins at human centromeres using next generation genome wide approaches - Chromosome elimination using CRISPR/Cas9 - Optimizing single molecule approaches to detect histone PTMs Please check our lab website here: https://www.nechemia-arbelylab.org/ |
| Roderick O'Sullivan, PhD | osullivanr@upmc.edu | * ADP-ribosylation dynamics during DNA replication * Epigenomic reprogramming of ALT cancer cells * identification of synthetic lethals targets for ALT cancers |
| Michael Palladino,PhD | mjp44@pitt.edu | This NIH funded project aims to identify the first ever treatment for a rare childhood neuromuscular disorder TPI Df. Studies include drug screening, toxicology and efficacy validation in human cell culture, patient fibroblasts and a new mouse model of TPI Df. |
| Francisco Schopfer, PhD | fjs2@pitt.edu | Drug development and new approaches to treat fatty liver disease. Development of anti-inflammmatory and anti-fibrotic drugs. Inhibition of STING pathway to modulate inmmune responses. Mass spectrometry-based lipidomic and pharmacokinetic studies. Development and targets of electrophilic drugs. |
| Adam Straub, PhD/Nadine Hempel, PhD | astraub@pitt.edu nah158@pitt.edu | A collaborative project between the Straub and Fazzari labs will focus on the molecular cellular, and in vivo signaling actions of novel nitroalkenes for treatment of Parkinson's disease. The joint project will utilize cell culture and in vivo model of Parkinson's disease. |
| Jesus Tejero Bravo, PhD | jet68@pitt.edu | Dr. Tejero’s research is focused on the biology of heme proteins. His main research goals include: i) to elucidate the cytoprotective mechanisms of the six-coordinate globins neuroglobin and cytoglobin, ii) the mechanisms of protein heme transfer, and iii) the development of heme-based antidotes for carbon monoxide poisoning. |
| Bennett Van Houten, PhD | vanhoutenb@upmc.edu | Work in our laboratory is focused on two major research interests: 1) Understanding the cooperation between DNA repair proteins in the base and nucleotide excision repair pathways; and 2) defining the role DNA Ligase 3/XRCC1 in genome stability. 1. Analysis of DNA repair proteins from single molecules to cells (R35ES031638), “Watching cooperative interactions between base and nucleotide excision repair proteins” is a NIH funded project. The goal of this project is to observe DNA repair molecules interrogating DNA for structural alternations in real time. The long-term goal of this project is to watch multiple DNA protein machines do work on DNA in cells and at the single molecule. To this end, we have developed a new method of single molecule analysis using nuclear extracts and a Lumicks C-trap that has combined optical tweezers, a five-chamber microfluidic flow cell and a three color confocal microscope to follow multiple proteins interacting at damaged sites. We are only one of 50 sites in the US that has access to this state-of-the-art instrument, which has opened new avenues of research for our group. We have studied UV-DDB, PARP1/2, XPC, AAG, OGG1, TDG, APE1, Pol B, and LIG3/XRCC1 2. Roles of Lig3 and XRCC1 Genes in Genome Stability. This NIH funded project (R01ES012512) in collaboration with Professor Alan Tomkinson (Univ. of New Mexico). Seeks to understand how DNA Lig3 works to seal nicks in nuclear and mitochondrial DNA. Studies with the LigI/III inhibitor L67 have shown that cells with mitochondria are more sensitive to the ligase inhibitor and that this sensitivity is due to inhibition of mitochondrial (mito) LigIIIα. Further studies revealed that inhibition of mito LigIIIα has markedly different effects in cancer and non-malignant cells |
| Jean-Pierre Vilardaga, PhD | jpv@pitt.edu | 1) Molecular mechanisms of G protein-coupled receptors (GPCR) signaling; (2) GPCR Druggability for osteoporosis |
| Qiming (Jane) Wang, PhD | qjw1@pitt.edu | Protein kinase D (PKD) as a novel target in neuroendocrine prostate cancer (NEPC): This is a NIH-funded project to investigate the potential of PKD as a therapeutic target for NEPC, an aggressive and treatment-resistant subtype of prostate cancer. Our study will explore PKD's role in regulating the cell cycle and its contribution to NEPC development. Using cell-based experiments and mouse models, we will also test small-molecule PKD inhibitors developed in Dr. Wang's lab. Our research aims to provide mechanistic insights into NEPC and identify new therapeutic strategies for this deadly disease. • Discovery and development of targeted therapeutics for ischemic stroke: This is an AHA-funded project aimed at identifying novel protein kinases and long non-coding RNAs (lncRNAs) as potential therapeutic targets for promoting neuronal survival and recovery after ischemic stroke. Using cellular and animal models, we'll design and evaluate cell-permeable peptides or small molecules targeting these kinases or lncRNAs. |
| Zhou Wang, PhD | wangz2@pitt.edu | Androgen receptor (AR) is the most important therapeutic target for prostate cancer, which is the most frequently diagnosed cancer and second leading cause of cancer death in USA males. Androgen deprivation therapy (ADT) or castration is the standard treatment for patients with metastatic prostate cancer. Unfortunately, patients on ADT will relapse with castration-resistant prostate cancer (CRPC), which is currently not curable. The major mechanisms leading to CRPC is reactivation of AR under androgen deprived condition. A necessary step leading to AR reactivation is AR localization in the nucleus because AR is a transcription factor. The potential rotation project will be to study 1) the mechanisms regulating AR levels in the nucleus, 2) how these mechanisms are dysregulated in prostate cancer cells, or 3) how nuclear AR level can be suppressed in CRPC. These research projects are fundamentally important and clinically relevant. |
| Lin Zhang, PhD | zhanglx@upmc.edu | 1) Mechanisms of cell death in cancer targeted therapy and immunotherapy (Funded by NIH grants R01CA236271 and R01CA247231) 2) Developing novel anticancer agents by manipulating cell death regulators in cancer cells (Funded NIH grants R01CA217141 and R01CA248112) 3) Targeting oncogenic stem cells for colon cancer prevention (Funded NIH grant R01CA203028) Training Technologies Used: Cell culture, molecular cloning, apoptosis assay, cell cycle analysis, DNA, RNA and protein analysis, gene-targeting, CRISPR/Cas9 RNAi, analysis of intestinal stem cells, analysis of animal tissue, assay development for library screening |
| Jonathan Beckel | jmbeckel@pitt.edu | The role of the endogenous antagonists SLURP1&2 on nicotinic acetylcholine signaling in the bladder epithelium. • Subcellular localization and effects of voltage-gated calcium channels on lysosomal exocytosis in the bladder epithelium. • Elucidating the mechanism of the anti-inflammatory effects of the engineered chloride channel EG3RF in the bladder epithelium. |
| Elise Fouquerel | elf115@pitt.edu | Role of PARP1 in the resolution of genomic R-loops: mechanisms of regulation of DNA-RNA hybrid recruitment through PARP1 activity. The project will involved cell and molecular biology as well as biochemistry and single molecule assays |
| Stacy Gelhaus, PhD | gstacy@pitt.edu | Changes in cellular metabolism using electrophilic fatty acids, * Electrophilic fatty acids as therapeutics in asthma, * Systemic changes in host and microbial metabolism in obesity associated asthma |
| Baoli Hu, PhD | baolihu@pitt.edu | Our lab is interested in understanding the molecular mechanisms of brain tumor evolution and developing new strategies for the treatment of these devastating diseases, particularly adult glioblastoma and pediatric medulloblastoma. The specific projects are: • Study a new protein complex (CHI3L1-Galentin 3-Galentin 3 BP) reprograming tumor immunosuppression in glioblastoma therapy (Chen et al., J Clin Invest. 2021). • Investigating the role of WNT5A Signaling in glioblastoma plasticity and treatment resistance (Hu et al., Cell, 2016; Wang et al., Cancer Cell, 2017). • Understanding how BAF60C/SMARCD3 orchestrates cerebellum development (Zou et al., Nature Cell Biology, 2023). • Illustrating molecular mechanisms of cancer cell metastatic dissemination in medulloblastoma (Zou et al., Nature Cell Biology, 2023) |
| Tony Kanai, PhD | ajk5@pitt.edu | 1) Reversing benign prostatic hyperplasia using soluble guanylate cyclase activators to ameliorate bladder outlet obstruction and lower urinary tract symptoms in aging mice; 2) Targeting p75 and TrkB/C neurotrophin receptors using small molecule drugs to treat spinal cord injury induced motor and autonomic dysfunctions; 3) Clearing chemotherapy-/radiation-induced senescent cells using senomorphic/senolytic agents as a strategy to prevent tumor recurrence; 4) Approaches to prevent or treat radiation cystitis with mitochondrial-targeted free radical scavengers. |
| Melanie Koenigshoff, MD,PhD | koenigshoffm@upmc.edu | Developmental pathways/stem cell biology for lung regeneration in COPD, aging hallmarks and extracellular matrix production in chronic lung disease, Regenerative drug screen |
| Adrian Lee, PhD | leeav@upmc.edu | RET as a target in brain metastasis. Estrogen receptor mutations in breast cancer. Liquid biopsies as a diagnostic in breast cancer. Single cell and nuclei analysis of breast cancer metastasis. Spatial transcriptomics of breast cancer heterogeneity |
| Steffi Oesterreich, PhD | oesterreichs@upmc.edu | Breast cancer research with a focus on treatment resistance and progression to metastatic disease |
| Abby Olsen | abby.olsen@pitt.edu | 1) Identifying novel glial therapeutic targets for Parkinson’s disease 2) Developing animal models for non-motor systems of Parkinson’s disease 3) Understanding alpha-synuclein induced gene transcription 4) Unpacking gene-environment interactions in Parkinson’s disease |
| Patricia Opresko, PhD | plo4@pitt.edu | We have projects investigating how oxidative and replication stress at telomeres causes genomic instability and premature cellular aging. We are using a chemoptogenetic tool to selectively induce oxidative DNA damage at telomeres to understand how this damage impacts telomere function and cellular health. We use complementary biochemical and cellular assays, fluorescence microscopy, proteomics screens, CRISPR-Cas9 gene knock out and other molecular approaches to identify proteins and pathways that protect telomeres from oxidative damage and replication stress. |
| Sruti Shiva, PhD | sss43@pitt.edu | 1) Elucidating mechanisms of platelet endothelial cross-talk in vascular disease; 2) Elucidating the role of mitochondrial fusion in pulmonary hypertension; 3) Understanding the role of myoglobin in the regulation of fatty acid metabolism in the heart and skeletal muscle |
| Thomas Smithgall, PhD | tsmithga@pitt.edu | Research in the Smithgall lab is focused on drug discovery and development targeting blood cancers and infectious diseases, with a particular emphasis of non-receptor protein tyrosine kinases. Current projects for students involve a wide variety of approaches and techniques, including recombinant protein kinase expression and purification, in vitro kinase assays, saturation mutagenesis to model evolution of kinase inhibitor resistance in cancer cell culture, development of novel assays to discovery allosteric (non-ATP site) kinase inhibitors, and structural biology and dynamics of multidomain kinase systems. |
| Wayne Stallaert | stallaert@pitt.edu | Studying how the tumor microenvironment influences cancer cell proliferation using single-cell, multiplexed imaging of breast, pancreatic and ovarian tumor samples. |
| Sina Tavakoli | tavakolis@upmc.edu | The focus of our lab is to develop novel imaging probes and therapeutics which target different subsets of monocytes and macrophages contributing to the pathogenesis of pulmonary (e.g., ARDS and lung fibrosis) and cardiovascular (e.g., atherosclerosis and myocardial infarction) diseases. We utilize a wide array of techniques to identify novel targets, such as chemokine receptors, and synthesize high-affinity binding molecules which may be used for in vivo molecular imaging (by positron emission tomography [PET]) and targeted delivery of drugs to specific subtype of cells in pre-clinical models and ultimately in humans. |
| Mary Torregrossa, PhD | torregrossam@upmc.edu | Potential rotation projects include investigating mechanisms by which nicotine enhances the reinforcing effects of THC, investigating neural mechanisms underlying increased alcohol seeking in females, understanding how chronic alcohol drinking alters sleep and circadian rhythms, and investigating the role of dopamine in the amygdala in learning. |
| Mohamed Trebak, PhD | trebakm@pitt.edu | Molecular mechanisms of mitochondrial and lysosomal calcium regulation/remodeling Calcium signaling networks in cancer and vascular occlusive diseases/Calcium channels in inflammation |
| Lianghui Zhang, MD, PhD | LHZHANG@pitt.edu | Rotation projects: 1) To explore lung vascular endothelial cells as antigen presented cells to signal immune cells to proliferate following influenza virus infection. 2) To identify the coronavirus (COVID 19) proteins to induce human lung vascular endothelial cell death. 3) To characterize the immune profile of endothelial-specific interferon alpha receptor knock out mice following influenza virus infection. |
[updated: 8/29/2023]