Gloria Borgstahl, PhD
Research Interests: The easiest way to learn about how a protein functions is to study its atomic structure. We use x-ray diffraction of protein crystals along with virtual reality to investigate proteins at the atomic level. Our focus is on proteins involved in the DNA double-strand break repair pathway with an emphasis on therapeutics to treat cancer. We are also researching the role of protons in the enzymatic function of superoxide dismutases using perdeuterated, microgravity-grown crystals (SpaceX, NASA, ISS) and neutron diffraction (Oak Ridge National Lab - Spallation Neutron Source).
For more information on Dr. Borgstahl: Website
Dalia ElGamal, PhD
Our research focuses on (i) understanding the pathogenesis of B-cell malignancies and (ii) evaluating novel targeted therapies for B-cell chronic lymphocytic leukemia (CLL) and Richter's transformation (RT) - an aggressive and incurable diffuse large B-cell lymphoma (DLBCL) that arises in the setting of CLL- with the overall aim of translating effective therapies to the clinic. Specifically, my laboratory aims to explore the dynamic cross-talk between malignant B-CLL cells and their microenvironment through a wide array of cell-based assays to identify "druggable" targets and pathways for therapeutic intervention which will be further evaluated utilizing the available mouse models of aggressive CLL/RT disease. Current studies in the laboratory are focused on epigenetic-based therapies including novel small molecule inhibitors of the bromodomain and extra-terminal (BET) family proteins, and their ability to modulate TME interplay in CLL. This is based on recent studies on the BET family protein “BRD4” which validated BRD4 inhibition as an epigenetic approach capable of downregulating multiple survival pathways in CLL. Importantly, these BRD4 profiling studies in CLL patient-derived tumor B-cells identified previously unrecognized targets of BRD4 implicated in CLL disease biology, progression and CLL-TME interactions including various chemokine/cytokine receptors and immune regulatory checkpoint molecules, indicating unique BRD4-mediated immunomodulatory properties which have yet to be fully investigated. Therefore, a major project in the laboratory aims to (1) investigate the immunomodulatory effects of BRD4 inhibition using in vitro approaches mimicking CLL-TME interplay; (2) study the ability of BRD4 inhibition to reverse immune dysfunction inherent to CLL; and (3) evaluate BRD4 inhibition in mouse models of aggressive CLL/RT, and its ability to reprogram the TME to disrupt protective niches and/or correct the immune defects commonly observed in this disease.
For more information on Dr. ElGamal: Website
Robert Lewis, PhD
Research Interests: Cells have important intracellular mechanisms for regulating cell growth and development. We are interested in determining what molecules are involved in this and how they interact to control cellular growth and gene expression. We are using molecular biology and biochemical techniques and mutant mouse models to study cell signaling mechanisms and how they function.
For more information on Dr. Lewis: Website
Amar Natarajan, PhD
Research Interests: Phosphorylation and de-phosphorylation reactions of cellular proteins are ubiquitous in nature and represent the molecular on/off switch that triggers innumerable signaling events mediated by phospho-specific protein-protein interactions. Our research interest focuses on the use of small molecules to perturb these phospho-specific protein-protein interactions as a first step towards understanding how cells exploit these interactions in signal transduction. Chemical probes for this effort are derived from natural products and the design of conformationally constrained mimics. Synthetic chemistry spearheads the research program, however, biology and computational methods are used synergistically in our quest for a better comprehension of the cellular events contiguous to phospho-specific protein-protein interactions.
For more information on Dr. Natarajan: Website
Youri Pavlov, PhD
Research Interests: The hallmark of biological systems is heredity, the ability to reproduce their properties in generations. It is based on templated reduplication of nucleic acids containing species-specific information. Heredity is made possible due to coordinated action of specialized protein machinery. Most organisms and cells need accurate reproduction to fulfill their biological duties, however in some, like for HIV viruses or B-cells, inaccurate reproduction is beneficial. The knowledge of atomic structure of the proteins and complexes of proteins with nucleic acids, maintaining the heredity, allows the unparalleled power of genetic analysis, disease prevention and gene therapy. We study the molecular basis of evolutionary strategies of heredity used by wide range of organisms, from viruses to humans.
For more information on Dr. Pavlov: Website
Pankaj K. Singh, PhD
Research Interests: A major project in the Singh lab aims to determine the metabolic interrelationship of pancreatic cancer cells with their surrounding microenvironment. They are also investigating the link between tumor metabolism and gemcitabine resistance in pancreatic cancer. By combining transcriptomics, metabolomics and proteomics we aim to identify the signaling networks that impart chemotherapy resistance to tumor cells. Other important projects include determining the metabolic regulation of cachexia in pancreatic cancer and the role of microRNAs in pancreatic cancer metabolism.
Joyce Solheim, PhD
Program Director and Professor
Dr. Solheim's laboratory is engaged in research related to immunology and cancer. In her laboratory, novel immunotherapy approaches for cancer treatment are being developed that stimulate the patient's own immune response against cancer. As part of these studies, her laboratory has collaborative studies underway that are exploring new nanomedicine delivery strategies for anti-cancer therapies. Her laboratory is also investigating the molecular mechanisms that regulate the recognition of malignant and infected cells by the immune system, as well as exploring the dual effects of certain proteins on immune function and on cancer cell growth and migration.
For more information on Dr. Solheim: Website
Jing (Jenny) Wang, PhD
Research Interests: Dr. Wang’s research focus is to characterize signaling pathways and molecular mechanisms of cancer development, metastasis and drug resistance. The laboratory goal is to identify and validate novel targets to improve cancer treatment.
Nicholas Woods, PhD
Research Interests: The Woods lab is focused on protein-protein interaction networks that regulate DNA damage repair as a mechanism of preventing cancer formation as well as sensitizing cancers to DNA damaging therapeutics. This research utilizes cutting-edge mass spectrometry and bioinformatic approaches to evaluate large scale protein interaction networks. The discovery of new molecular interactions important for cancer biology has the potential to identify novel targets for therapeutic interventions.