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An NCI-designated Comprehensive Cancer Center, affiliated with the University of Pittsburgh School of Medicine
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My broad areas of expertise include human hematopoietic and leukemia stem cell biology. My research is focused on (1) understanding miRNA control of the molecular and signaling pathways that direct the cellular fate of normal and malignant human hematopoietic stem and progenitor cells and (2) elucidating the developmental, cellular and molecular origins of adult and pediatric leukemia. My research is guided by multi-omic analysis of primary patient samples/tissues and utilizes functional genomics in combination with xenotransplantation into immune deficient mice.
The laboratory studies the molecular basis of breast cancer development and resistance to therapy, with the goal to improve precision medicine and outcomes for breast cancer patients. The laboratory employs a systems biology approach, utilizing a combination of single cell and bulk sequencing, computational methods, and biological models to identify and validate new drivers and therapeutic targets. Hypotheses are tested in vitro and in vivo and then moved to clinical trials. The majority of studies incorporate analysis of human specimens, in collaboration with a large network of clinicians and nurses. This includes computational analysis and modeling of large biomedical and genomic datasets including electronic health record data. A major goal is new model development including patient-derived organoids and patient-derived xenografts. A major focus of the laboratory is identifying mechanisms of resistance to endocrine therapy, and new approaches to blocking breast cancer metastasis through precision medicine. This includes the study of estrogen receptor (ESR1) mutations and fusions and synergism with growth factor pathways. Methods include liquid biopsies and use of a rapid autopsy program,. A special focus is on the understanding of invasive lobular cancer (ILC), the second most common but understudied histological subtype of breast cancer. The laboratory has a very strong training environment, with attention to diversity and inclusion and each individuals’ successful career development. One of the top priorities is to maintain a healthy lab environment, ensuring high productivity and rigor.
Many noncoding (nc)RNAs execute diverse cellular functions and are equally important as their coding counterparts. In recent years, owing to the development of cutting-edge technology, such as next-generation sequencing, the detection of ncRNAs and elucidation of their functions have been facilitated. However, compared to the large number of identified ncRNAs, only a minute fraction has been ascribed a specific function, as more and more surprising aspects regarding their mode of action are being uncovered.
Our lab studies the molecular function of two enigmatic ncRNAs from the Epstein-Barr virus (EBV) called EBER1 (EBV-encoded RNA 1) and EBER2. EBV is an oncogenic gamma-herpesvirus with a prevalence of over 90% in the human population and is associated with several types of cancers, such as lymphomas and carcinomas. We apply modern RNA techniques as well as refine existing tools to uncover the modes of action of these viral transcripts. Utilizing these methodologies, our work has revealed a role in transcription regulation for EBER2 and how it ensures efficient viral replication.
A second focus of research is centered on studying the genome architecture of influenza viruses. Given the fact that influenza viruses harbor a genome consisting of RNA, many of the RNA-centric tools we employ to study ncRNAs can be applied to examine how the viral RNA genome is organized during replication. Utilizing these methodologies, we have uncovered molecular details of how the genome associates with viral proteins and how long-range RNA-RNA interactions are essential for viral packaging.
We use live-cell experiments and mathematical models to understand how single cells process information in inflammatory diseases and cancer. To decide between irreversible cell fates such as growth, differentiation or death, cells process information about their environment through a network of molecular circuits. Our research combines principles of systems and synthetic biology with large-scale data to understand how information flows through these circuits. By observing input-output relationships in the same cell using microfluidics, live-cell dynamics and single-molecule microscopy, we aim to decode the ‘language’ of signaling dynamics and develop mathematical models of information flow with single-cell resolution. Our ultimate goal is to understand how population-level responses emerge from single-cell heterogeneity and to rationally manipulate cell fate decisions in disease.
My research interests are centered on structuring and delivering health information through an informatics-based approach to diverse demographic groups, with a particular focus on minority populations. I have actively involved community residents in my research, conducting assessments to understand their needs and contexts. This approach aims to empower individuals to manage their own health through targeted health communication interventions. Methodologically, my work is grounded in extensive experience with mining big data, allowing me to uncover hidden relationships between various agents.
Currently, I am at the forefront of the NIH-funded study HELPeR (Health E-Librarian with Personalized Recommendations, R01 LM013038). This project is committed to assisting ovarian cancer patients as they navigate online information resources.
Michele D. Levine, PhD, a licensed clinical and health psychologist, is Professor of Psychiatry, Psychology and Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh. Dr. Levine’s program of research focuses on relationships among health behaviors and mental health during pregnancy and the postpartum period. Dr. Levine also directs a T32 postdoctoral training grant and an affiliated clinical psychology internship training program at Western Psychiatric Hospital, both of which support clinical research training.
The main research interest in Dr. Gang Li's lab is to understand the molecular mechanisms underlying the contribution of disease-associated, non-coding functional SNPs to aging-related diseases by focusing on Alzheimer's disease and atherosclerosis. Dr. Li's lab has developed multiple techniques such as Reel-seq, SNP-seq, FREP/SDCP-MS and AIDP-Wb to identify the causal SNPs as well as the SNP-bound regulatory proteins based on genome wide association studies (GWAS). The lab's goal is to use human genetics (GWAS) as a guide to identify new drug targets and, ultimately, to apply these findings to develop allele-specific precision drugs for aging-related human diseases as well as other diseases.
I am an early-career researcher with a strong passion for cancer-related research. The goal of the my lab is to unravel the molecular and cellular mechanisms driving immunosuppression in the tumor microenvironment, with a particular focus on CD8+ regulatory T cells. We will leverage cutting-edge technologies, mouse tumor models and patient-derived specimens to drive scientific advancements in the field of cancer immunology and human immunology.
Epstein-Barr virus (EBV) is the causative agent of nasopharyngeal cancer (a type of head and neck cancer), stomach cancer and several types of lymphomas. Each year 200,000 cancers worldwide are caused by EBV. The presence of EBV in cancer cells also provides a unique opportunity for targeted therapy by forcing tumor cells to reactivate latent EBV. The Li lab is focusing on understanding the molecular mechanisms by which viral and host factors control the transition of EBV from latency to reactivation with a goal of developing novel therapeutic strategies to cure EBV-associated cancer.
Dr. Li has broad knowledge in medicine, biology, and drug and gene delivery and has established a strong research program centered at the interface of biology and biotechnology.
His lab has developed several novel delivery systems that are aimed to solve major issues in his fields through improved understanding of the fundamental aspects of drug formulations and comprehensive structure-activity relationship (SAR) study. His group proposed the concept of “new amphiphilic surfactants with interfacial drug-interactive motif”, which has helped to solve the problem of formulating many “hard-to-formulate” drugs (Molecular Pharmaceutics, 2013; Biomaterials, 2015). Another breakthrough from Dr. Li’s group is the development of ultrasmall nanocarriers for improved cancer treatment (Theranostics, 2020; Biomaterials, 2021, Materials Today, 2023). Dr. Li’s group has discovered that covalent coupling of nucleosides-based drugs (such as gemcitabine, azacitidine, cytarabine, decitabine, and others) into an amphiphilic polymeric carrier led to a drastic reduction in sizes from ~150 to ~15 nm. This system is highly effective in codelivery of various front-line water-soluble and water-insoluble drugs. Due to its ultrasmall size, this technology holds promise in overcoming the challenge of ineffective tumor accumulation and penetration seen in cancer patients. More recently, his group has developed another new delivery system that is highly efficient in tumor accumulation through targeting CD44 on tumor endothelial cells (ECs) (Nature Nanotechnology, 2023). This system is suitable for delivery of small molecules or nucleic acids alone or codelivery of both types of therapeutics.
In addition to the development of improved delivery systems, Dr. Li’s group has sought to uncover new mechanisms involved in resistance to chemotherapy and/or immunotherapy. His lab has recently identified glutamate metabotropic receptor 4 (GRM4) as a novel negative regulator in antitumor immunity in multiple tumor models (Science Advances, 2021). More recently, Dr. Li’s group has identified Xkr8 as a novel gene that is critically involved in chemotherapy-induced immune suppression and cancer relapse, suggesting a new combination therapy via targeting Xkr8 (Nature Nanotechnology, 2023).
Prior to joining Pitt SPH, I served as the Associate Director for Population Sciences of the Tulane University Cancer Center for 15 years. I represented Tulane on the NCI GMAP region 2 consortium. My cancer-related research focuses on cancer health disparities locally and globally with a special emphasis on the Caribbean. Of special interest is the role exposures to chemicals and non-chemicals stressors play in cancer development. Additionally, I am a board member of the Intercultural Cancer Council (ICC), and appointed chair of the board effective January 2024.
The Liu Lab studies several medically important bacterial virulence factors, including anthrax toxins, in bacterial pathogenesis. Through investigating the interactions of these protein toxins and their mammalian hosts, we are interested in discovering the toxins’ molecular targets and understanding the molecular mechanisms of pathophysiology. We study how these toxins alter key signal transduction pathways, in particular the RAS and ERK pathways, in cancer cells and tumor stromal cells, and we use the knowledge obtained to design and develop novel bacterial toxin-based anti-tumor drugs with high tumor specificity. We are also interested in using this approach to design and develop novel biological-based therapeutics to selectively eliminate senescent cells.
Dr. Lohmueller’s laboratory focuses on engineering synthetic receptors and gene circuits to improve adoptive cell therapies to treat cancer. Two major goals of the lab include enhancing receptor targeting specificity as well as remediating suppression of the anti-tumor immune response. One area of technology development is engineering universal chimeric antigen receptors (CARs) capable of multi-antigen targeting and tunable receptor activity. These receptors potentially allow for treating a variety of cancers, while avoiding cancer relapse, and alleviating therapy-related toxicities.
Dr. Lotze's primary area of research is broadly in tumor immunology, particularly the role of cellular therapy using dendritic cells, T cells, and NK cells. His current research interests include the further identification of clinical biomarkers and surrogates in the setting of cancer, the role of cell death pathways and autophagy, the nuclear protein high molecular group B1 [HMGB1] and other Damage Associated Molecular Pattern Molecules [DAMPs] in tissue injury, repair, and cancer. He is currently preparing major reviews on the role of costimulation as part of the therapeutic approach to cancer, integrating cancer biology and tumor immunology.
Dr. Low is a clinical health psychologist focused on using consumer mobile technology including wearable devices and smartphones for remote monitoring of symptoms and functioning during cancer treatment. Her team is interested in using these real-world data to predict clinical outcomes, to support patient self-management and patient-provider communication, and to personalize behavioral interventions aimed at optimizing quality of life.
Jason J. Luke, MD, FACP, is an Associate Professor of Medicine at the University of Pittsburgh and UPMC Hillman Cancer Center where he is Associate Director for Clinical Research and the Director of the Immunotherapy and Drug Development Center (Phase I). Dr. Luke specializes in early phase drug development for solid tumors (particularly novel immunotherapeutics and biomarkers of immunotherapy activity) as well as the management of melanoma.
Dr. Luke is one of the foremost international investigators in the realm of immuno-oncology, having led clinical trials of immunotherapies including but not limited to anti-PD1/L1, CTLA4, many secondary checkpoints, bispecific approaches (checkpoint, CD3 and cytokine), metabolism modifiers (IDO, A2Ar/CD73/CD39 and arginase), innate agonists of STING, TLRs and oncolytic virus as well as solid tumor cellular therapies (TCRs and CART). In melanoma, Dr. Luke has designed and led two practice changing trials determining the role of anti-PD1 + CTLA4 after initial anti-PD1 failure (compendium listed in the NCCN) and altering the landscape of melanoma oncology practice across dermatology, surgery and medical oncology via establishment of modern adjuvant therapy with anti-PD1 for node negative stage IIB/C disease (leading to FDA/EMA approval). Dr. Luke has been a major contributor toward the investigation of radiation and the microbiome in relation to cancer immunotherapy. Dr. Luke’s major translational research focus leverages large scale informatics to advance cancer immunotherapy.
Dr. Luke received his MD from Rosalind Franklin University of Medicine and Science in Chicago. He then pursued internship and residency at the Boston University Medical Center followed by medicine and medical oncology fellowships at Weill Cornell Medical College and Memorial Sloan-Kettering Cancer Center in New York City. Following fellowship, Dr. Luke was a tenure-track, Type 1 Instructor in Medicine at Harvard Medical School as well as Staff Physician at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston. Thereafter Dr. Luke was an Assistant Professor at the University of Chicago.
Dr. Luke is currently Senior Editor at Clinical Cancer Research, Section Editor at the Journal for Immunotherapy of Cancer and Skin Cancer Section Editor for the American Cancer Society journal Cancer. Dr. Luke is actively involved in several professional societies including SITC (where he sits on the Board of Directors), AACR, ASCO, and the Society for Melanoma Research, having served on the scientific program committees for each. Dr. Luke leads an R01 funded laboratory, he is co-PI for the Pittsburgh UM1 LAO and is project 3 clinical co-leader of the Pittsburgh Skin Cancer P50 SPORE, in addition to multiple private and state awards. Dr. Luke has received several awards for research and clinical care including the Melanoma Research Foundation Humanitarian Award, Crain’s 40 under 40, DOD Career Development Award, Paul Calabresi Career Development in Clinical Oncology Award (K12), ASCO Merit Award as well as Young Investigator Awards from the Melanoma Research Alliance, the Cancer Research Foundation and the Conquer Cancer Foundation of ASCO.
Dr. Luo's research is in the area of genome and gene expression studies of malignancies, especially in understanding how liver and prostate cancers obtain invasive and metastatic capabilities. Dr. Luo's laboratory in the past has primarily focused on the isolation and characterization of genes which are inactivated in liver and prostate cancers. His laboratory is currently focusing on characterizing oncogenic fusion genes in human malignancies and developing fusion gene targeting tools to diagnose and treat human cancers. Dr. Luo is also interested in developing long-read sequencing techniques to characterize isoform switches and mutation isoform expressions in human cancers.
Dr. Luu has a broad background in medicine and epidemiology, with specific training and expertise in the molecular and genetic epidemiology of cancer as well as large population-based studies. His main research focuses on etiological role of genetic factors, lifestyle factors, and environment exposures, particularly chronic inflammation, in the development of cancer as well as their impact on prognosis of cancer patients, particularly patients with gastrointestinal cancers such as colorectal cancer, pancreatic cancer and liver cancer.
