Faculty | Research interest/projects | |
---|---|---|
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. |
Rannar Airik, PhD | airikr@pitt.edu | Our lab focuses on identifying the genetic and molecular mechanisms of chronic kidney disease (including renal ciliopathies), to develop therapies against this condition. In our work we use transgenic mouse models, patient derived cells and various biochemical/proteomics assays to dissect the disease mechanisms. Current projects include: 1. Dissecting the role of DNA damage in chronic kidney disease. 2. Investigating the mechanisms that drive acute kidney injury to chronic kidney disease transition. 3. Use of senolytic therapy to counter chronic kidney disease. |
Timothy Burns, 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; targeting metabolism in oncogene driven lung cancer); and 2) elucidating mechanisms of resistance for targeted inhibitors to develop rationale therapeutic combinations that can be tested in the clinic 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 and therapeutic resistance. 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. The third line of research in my lab is focused on lung cancer brain metastases, and we are exploring whether targeting the HGF-MET-TWIST1 pathway or downstream metabolic pathways 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. Finally, we have undertaken an investigator-initiated trial to test whether we can treat brain metastases with MET TKIs. |
Michael Butterworth, PhD | michael7@pitt.edu | The research focus of the lab is the (sex-specific) role of microRNAs in renal sodium handling. We use KO and gain-of-function mouse models with primary and engineered cell lines to investigate the hormonal regulation of microRNAs in the kidney. Findings are linked to in vivo physiologic regulation of sodium transport and blood pressure. These studies aim to uncover novel pathways to account for sex-specific differences in hypertension. See more |
Yuan Chang, MD and Patrick S. Moore, MD, MPH | yc70@pitt.edu psm9@pitt.edu | Our lab (jointly co-directed with Dr. Yuan Chang) seeks to identify new human cancer viruses and to understand how these viruses initiate cell transformation and tumorigenesis. To this end, we discovered the viruses causing Kaposi sarcoma (Kaposi sarcoma herpesvirus, KSHV) and Merkel cell carcinoma (Merkel cell polyomavirus, MCV) using molecular techniques. Our laboratory is currently seeking to new proteomic methods that may help inform us on the presence of undiscovered viruses in cancers thought to have an infectious etiology. See more |
Christopher Cunningham, PhD | cunningc@pitt.edu | The Cunningham Lab is interested in understanding the neural and sensory biology of the vertebrate auditory system. Many unique and highly specialized proteins with exquisitely precise subcellular localizations are critical for each step of sound processing. Hearing loss is the most common sensory deficit, and multiple forms of hearing loss involve aberrant proteostasis—improper assembly, trafficking, and/or regulation of key auditory proteins. We utilize mouse models of human deafness for our experiments. The similarities between the rodent and human auditory systems allow for a panoply of experimental manipulations that aim to uncover basic biological mechanisms and translational insights relevant for human health. The lab utilizes cutting-edge techniques including the generation and analysis of novel genetic mouse models combined with biochemistry, molecular biology, histology, viral vectors and high-resolution fluorescent microscopic imaging. Ultimately, we hope to utilize our findings toward the development of new therapies for hearing loss and deafness. To this end, we are very interested in developing gene therapy strategies that can treat hearing loss. More info: thecunninghamlab.com |
Susana da Silva, PhD | dasilvas@pitt.edu | The research in our lab is centered on a small but highly specialized area of the retina named fovea. The fovea is a high acuity area responsible for our ability to read, drive and recognize faces. We are very interested in deciphering the molecular underpinnings of fovea development and subsequently establish new experimental models of human foveal diseases. Our lab uses a multidisciplinary research program based on multiple model systems, such as chick embryos and human retinal organoids, combining classical embryological manipulations and state of the art genomic, molecular (multiomics) and human iPSCs 3D culture techniques. |
Wei Du, MD, PhD | duw@upmc.edu | Our lab studies the underlying mechanisms by which the normal and abnormal hematopoiesis are regulated. We use DDR deficient mouse model, human xenograft model to identify potential therapeutic targets for leukemia treatment. We are also interested in understanding hematopoietic stem cell (HSC) and Bone marrow niche interaction. Potential projects include: 1) Define the molecular and functional collaboration between a major cell signaling (FA) pathway and immunometabolic regulation in HSCs; 2) Target stem cell-niche interaction for improved therapy for patients with bone marrow failure and leukemia; 3) Study a novel interplay between DDR and immune responses in FA leukemogenesis; 4) Study on the systemic immune effects of persistent DNA damage using mouse and human models of DNA repair deficiency and aging; 5) Molecular mechanism and therapeutic potential of synthetic lethal targeting our newly identified PRMT5-CtIP-FANCD2 complex in homologous recombination repair-competent cancers; and 6) Mechanistic and functional elucidation of the role of a novel paracrine Wnt5a-Prox1 signaling axis in regulating HSC regeneration under conditions of injury and aging. |
Mo Ebrahimkhani, MD |
mo.ebr@pitt.edu | Laboratory for Synthetic Biology and Regenerative Medicine led by Dr. Ebrahimkhani combines synthetic biology, systems biology and stem cell engineering to advance regenerative medicine, develop new therapies while also study human development. See more |
Miguel Brieño-Enriquez | MIGUELBE@pitt.edu | During early embryonic development, and particularly during the initial steps of organogenesis, cell, tissues, and organs are separated by wide intracellular spaces filled by extracellular matrix (ECM). The extracellular matrix (ECM) plays pivotal roles in cell self-renewal, fate, death and signaling to regulate diverse function including migration, proliferation, and differentiation. One of ECM components is hyaluronan (HA), a ubiquitously expressed glycosaminoglycan. HA can be detected in the organism in its high-molecular-weight (HMW) form. HMW-HA has been shown as a critical element during the phases of separation, migration, and colonization of the gonads by precursors of the gametes, the primordial germ cells (PGCs). Little is known about how HA regulates the number of PGCs, their differentiation, meiotic entry and establishment and maintenance of ovarian reserve. In the proposed research, we will test the overarching hypothesis that the stromal microenvironment of the fetal ovary, including an HA-rich matrix, regulates the establishment and maintenance of the ovarian reserve and reproductive longevity. To test this hypothesis, we will use the naked mole-rat (Heterocephalus glaber, NMR), mouse and human as a model. To evaluate the role of vHMW-HA we will use transgenic mice that express the nmrHas2 in the different compartments/cells of mouse ovary using cell-specific Cre alleles. Evaluation of the conserved effect of high molecular hyaluronan in ovarian development we will evaluate the localization of HA in human ovaries, the total levels, and the gene expression. Taking this all together, this project will show the regulatory role of HA in the stromal microenvironment of the fetal ovary, and its functions in the establishment and maintenance of the ovarian. |
Farzad Esni, PhD | farzad.esni@chp.edu | Pancreatic Development and Regeneration Diabetes and pancreatic cancer are two major diseases linked to the pancreas. Type-1 diabetes is a syndrome defined by high blood glucose levels caused by reduction in number of insulin producing beta cells. A cure for diabetes will be achieved through replacement of beta cells. Pancreatic cancer is an almost uniformly fatal disease. Understanding the biology of pancreatic cancer and particularly, its precursor lesions, are prerequisites for the development of more sensitive early detection biomarkers and more potent therapeutic and chemopreventive strategies. See more |
Shou-Jiang (SJ) Gao, PhD | gaos8@upmc.edu | The Gao lab is part of the Cancer Virology Program (CVP) in the UPMC Hillman Cancer Center. The lab primarily studies the mechanism of infection and oncogenesis of cancer viruses. The student will be exposed to molecular virology, cancer biology, cancer metabolism, epigenetics, epitranscriptomics, interactions of cancer cells with tumor microenvironment and immune cells, inflammation, microbiome and cancer therapy. The lab closely collaborates with computational biologists, particularly Dr Yufei Huang, who is also in CVP, allowing the development of novel systems approaches for dissecting complex biological questions, including the recent development of novel analytic tools for spatially-resolved single cell transcriptomics. Recent works have identified novel tumor suppressive functions of an arginine sensor CASTOR1, which regulates both tumor and immune cells. Ongoing works are examining the functions of CASTOR1 in other types of cancer including lung cancer and HPV-associated head and neck squamous cell carcinoma, and innate and adaptive immunity in models of colitis and colon cancer. See more |
Arjumand Ghazi, PhD | ghazia@pitt.edu | With a rapidly aging global population, it is a public health issue of great significance. Research on aging not only helps us understand a fundamental and fascinating biological process, but it may also be the least expensive and fastest path to simultaneously targeting multiple age-associated pathologies. Recent discoveries have suggested that aging is not just the result of stochastic cellular damage. Instead, it is strongly influenced by genes that appear to be conserved in their longevity functions, from worms to humans. Such longevity genes are the focus of our lab’s research. Please visit Ghazi Lab: Molecular Genetics of Aging to learn more. |
Aditi Gurkar, PhD | agurkar1@pitt.edu | Our lab is interested in understanding what drives age-related diseases and aging. The goal is to define interventions that can improve health and quality of life. Our lab uses C. elegans, mice, induced pluripotent stem cells (iPSc) and patient samples to understand the basic biology of aging. Potential projects include: 1. Role of lipid metabolism and epigenetics in aging. 2. Understanding the role of DNA damage-induced cellular senescence in cardiovascular disease. 3. Integration -omic and causal inference to translate ‘aging’ from bedside to bench. Techniques commonly used in the lab vary from cell culture, molecular biology, immunofluorescence, single cell RNA-seq and data integration (metabolomics, lipidomics, RNA-seq), phenotyping mice including frailty and skeletal muscle integrity. |
Erin Kershaw, MD | kershawe@pitt.edu | Our mission is to forward the understanding and treatment of obesity and related metabolic disorders (i.e. insulin resistance, glucose intolerance, diabetes, dyslipidemia, cardiovascular disease). A major focus includes disorders of “fat” (i.e. adipose tissue, lipids). We use a multidisciplinary approach that combines basic and translational research with clinical expertise. Our goal is to develop better strategies for prevention and treatment of obesity and its complications. See more |
Bernhard Kuhn, MD | bek59@pitt.edu | While much is understood about the mechanisms of the human heart, when it is examined on the cellular and molecular level, many mysteries remain. Notably, these specialized contractile cells, called cardiomyocytes, are exceptional in that they lack the ability to replicate and proliferate, processes that are necessary to repair tissue damage and restore normal function. Our innovative work has already provided insight into the growth mechanisms of these cells. The Kühn Lab’s long-term goal is to regenerate human hearts. This involves developing therapies that can help the heart muscle, the myocardium, to heal itself – to recover from a heart attack, or to help it restore a congenital heart defect to normal cardiac function without requiring surgery. See more |
Adrienne Lee, PhD/ Steffi Oesterreich, PhD | leeav@upmc.edu sto16@pitt.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/ |
Nara Lee, PhD | nara.lee@pitt.edu | Research in the Lee lab focusses on elucidating the molecular mechanism of how noncoding RNAs expressed by Epstein-Barr virus facilitate viral replication. To this end, we apply techniques entailing next-generation sequencing to examine RNA-RNA, RNA-protein, and RNA-chromatin interactions. |
Guang Li, PhD | guangli@pitt.edu | The Li lab has three research areas. 1) Heart development. We are studying the temporal and spatial molecular signatures of the developing hearts using single cell multiomics and spatial omics. 2) Heart organoid and spheroid: We are developing methods to generate a four-chambered hearts in dish using human iPSC and primary cells. 3) Heart regeneration. Multiple heart injury models including cell ablation, cryoinjury, and LAD models are used to study the heart regeneration process in embryonic and neonatal mice. Also Post-GWAS functional studies to understand the mechanism of Atherosclerosis and Alzheimer's disease for drug development. |
Nathan Lord, PhD | ndlord@pitt.edu | Developing embryos must orchestrate the fates and movements of their cells with precision. However, precise control is no easy feat; genetic mutations, unexpected environmental perturbations and noisy signaling all threaten to scramble communication. Despite these challenges, development is remarkably robust. How do developing systems ensure precise pattern formation? How are mistakes corrected when they occur? Can we learn to engineer synthetic systems to have the reliability of developing embryos? Answers to these questions must span multiple scales, from signaling responses in individual cells to collective cell movement and morphogenesis. Our lab will tackle these questions with a combination of optogenetic manipulation, quantitative microscopy, computational modeling and classical embryology. Over the long run, we hope to learn the mechanistic principles that enable embryos to avoid and correct errors in development. See more |
Yael Nechemia-Arbely, PhD | arbelyy@upmc.edu | We study mechanisms of epigenetic assembly, maintenance and propagation of human centromeres that are essential for faithful chromosome segregation during mitosis. Chromosome missegregation can lead to aneuploidy which is a hallmark of many human tumors. We use cutting edge genomic approaches (ChIP-sequencing, CUT&RUN, long-read Oxford nanopore sequencing, Repli-seq, and Hi-C combined with molecular biology and microscopy to determine how centromeres are structured and how they are epigenetically maintained and propagated across the cell cycle. Please check our lab website here: https://www.nechemia-arbelylab.org/ Possible Rotation Projects include: - 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 |
Opresko, Patricia, PhD | plo4@pitt.edu | Our lab studies DNA damage and repair at telomeres and roles for telomere damage in human diseases, aging and cancer. We are focused on three main areas: 1) how oxidative and genotoxic stress accelerates telomere shortening and loss, 2) defining the cellular pathways that preserve telomeres in the face of DNA damage and 3) determining the consequences of telomere damage on telomere function, cellular function and organisms health. Ultimately, we hope to develop new strategies that preserve telomeres in healthy cells and delay aging-related diseases including cancer, or that conversely deplete telomeres in cancer cells to stop their proliferation. Please visit http://www.opreskolab.com |
Kyle Orwig, PhD | orwigke@upmc.edu | The lab develops and tests stem cell and tissue transplant technologies as well as gene therapy approaches for treating the most challenging infertility diagnoses (no eggs, no sperm. |
Andrey Parkhitko | aparkhitko@pitt.edu | The Parkhitko lab is interested in how metabolism is reprogrammed with aging and how age-dependent metabolic changes can be targeted to extend health- and lifespan. We use both Drosophila and mice to search for new metabolic pathways connected to the aging process, explore how these metabolic pathways regulate aging, test whether targeting these pathways late in life would extend healthspan, and create new tools to manipulate/study these pathways |
Edward Prochownik, MD, PhD | procev@chp.edu | My laboratory has a long-standing interest in the oncogenic Myc transcription factor and its role not only in cancer but in normal growth and development as well. We have recently been able to overcome the long-known embryonal lethality of Myc KO mice by inactivating the gene soon after birth thereby allowing us to determine how Myc impacts normal growth and development. By following the mice over their entire life span, we have shown that they develop a marked premature aging phenotype. Surprisingly however, they live longer than control mice due to the fact that they are unable to develop tumors due to their lack of Myc. RNAseq analysis indicates that many Myc target genes are altered in aging humans, thereby indicating that the MycKO mouse represents an excellent model of human aging. Current efforts are aimed at understanding the molecular, biochemical and metabolic basis for these unexpected phenotypes. A second project concerns the use of a mouse model for the most common pediatric liver cancer, hepatoblastoma (HB). Using a variety of molecular and bio-informatics-based tools we have identified a group of 22 genes that are invariably dysregulated in mouse and human HBs, irrespective of cause, stage, growth rate or histologic subtype. They are also highly predictive of survival in human HB. We are currently over-expressing these genes using Sleeping Beauty vector-mediated over-expression or Crispr-mediated knockdown in vivo to determine whether we can alter the natural history of HBs, thus potentially identifying novel means of therapeutic intervention. |
Donghun Shin, PhD | dhuns@pitt.eduong | The Shin lab uses zebrafish as a model organism to understand the cellular and molecular mechanisms of liver regeneration, focusing on the plasticity of two main cell types in the liver, hepatocytes and biliary epithelial cells (BECs). Depending on the severity and type of liver injury, hepatocytes convert to BECs; BECs convert to hepatocytes. A better understanding of these phenomena will contribute to better strategies to augment innate liver regeneration in patients with severe liver diseases as therapeutics. See more. |
Michael Tsang, PhD | tsang@pitt.edu | 1) Modeling human congenital heart disease in zebrafish 2) Understanding the molecular mechanism of heart regeneration 3) Modeling RASopathy using genetic code expansion. |
Bennett Van Houten, PhD | bev15@pitt.edu | Dr. Van Houten’s laboratory is doing cutting-edge research in two fundamental areas of biology, namely, how cells maintain genome integrity and generate energy. More specifically, his group studies the structure and function of DNA repair enzymes at the single molecule level, and the role of mitochondria in cancer and neurodegenerative diseases. Dr. Van Houten’s laboratory is currently supported by a NIEHS Revolutionizing Innovative Visionary Environmental health Research (RIVER) Award R35 ES031638 which uses state-of-the-art single molecule approaches, including atomic force microscopy and real-time fluorescence microscopy to follow fluorescently tagged-DNA repair molecules as they interrogate DNA for structural alternations in real time. The long-term goal of this project is to watch multiple protein machines do work on DNA at the single molecule level in purified systems, nuclear cell extracts and in living cells. |
Xiaosong Wang, MD, PhD | xiaosongw@pitt.edu | The research project for this rotation will interface the “dark side” of cancer genetics with cancer immunology. Specifically, we will investigate a cryptic class of adjacent gene rearrangements in more aggressive and therapy-resistant forms of breast cancer and/or other solid tumors and examine their function in cancer progression and/or immunotherapy resistance at individual level or at system level. The student may choose to systematically characterize the function of adjacent gene rearrangements in immunotherapy resistance using clinical trial datasets, experimentally validate newly discovered genetic targets, characterize their molecular basis, elucidate their clinical significance using patient samples, confirm their role in tumor progression, immune disfunction, or therapy resistance, pinpoint their mechanistic basis, and explore potential clinical applications. For more information, please visit our website: https://www.cagenome.org/lab |
Xiangyun Wei, PhD | weix@upmc.edu | Topic 1: Orientational cell adhesions for tissue morphogenesis Topic 2: Transcriptional regulation of polarity genes See more |
Yvette Yien | yieny@pitt.edu | Our lab is interested in the interplay between iron metabolism and development. Using an innovative multidisciplinary approach using multiple model systems (mouse, zebrafish, yeast and cell biology), we are identifying tissue specific roles of mitochondrial homeostasis proteins that couple iron metabolism with the specific needs of cells, with an eye towards identifying pathological and therapeutic mechanisms of iron dysregulation in specific tissues. Secondly, we are working to interrogate the mechanisms by which iron functions within developmental signalling pathways and cell fate. Lastly, we are actively attempting to identify hematopoietic and iron metabolism adaptations in the pregnant female's bone marrow (using mouse models) as they progress through pregnancy. |
Bokai Zhu, PhD | bzhu@pitt.edu | We are a multidisciplinary lab that use quantatitive system biology approach to study stress response, proteostasis, biorhythms in the regulation of metabolism and aging, with both basic research and disease implication. Some of the key words related to our research are: xbp1, ultradian and circadian rhythm, epigenetics, proteostasis, transcription, phase separation, stress response. fatty liver, aging and senescence. Whether you are into basic research or translation research, this is the lab you should join. Please visit https://www.bzhulab.com/ and follow me @LabZhu on twitter. |
[updated: 5/22/2024]