Dr. Balaz’s research is oriented towards the development of experimental and computational methods for determining drug disposition and receptor binding. In disposition, his lab performs experimental measurements using (1) surrogate phases to find structural determinants of transbilayer transport rates and accumulation in membranes and triglyceride phases, and (2) binding to prevalent human proteins such as albumin and extracellular matrix components. The data is used to develop structure-based models for predicting the volume of distribution and other pharmacokinetic characteristics. One of the major goals of this work is to find ways to tailor drug structures for limited distribution, thereby reducing the cytotoxicity of drugs such as those used in treating some cancers or arthritis.
Dr. Dearborn’s research focuses on development neurobiology in the fruit fly (Drosophila) in three primary areas: 1) The elucidation of vitamin D3 up-regulated protein 1 (VDUP1) tumor suppressor function during brain development, including VDUP1’s role in neural stem cell biology, 2) Hedgehog (Hh)-dependent regulation of VDUP1 in cell proliferation, including how tumor cell-specific differences in Hh signaling affect pharmacological treatment strategies, and 3) Molecular characterization of Eph receptor signaling pathways, which regulate axon guidance, vascular growth, and tumorigenesis. The lab emphasizes molecular-genetic approaches in these studies, each with clinical and translational relevance.
Associate Professor and Director of Research
Dr. Hass’ research integrates synthetic organic chemistry, pharmaceutical formulation and stability, biochemical assays, medicinal chemistry, and pharmacology. Her laboratory provides training opportunities for students in the areas of drug synthesis, pharmaceutical formulation, topical drug delivery, and assessment of drug efficacy. A major area of focus is the synthesis and activity of new drugs for use as topical agents to treat skin diseases. One group of novel co-drugs is designed to replenish natural antioxidants in the skin for enhanced and extended photoprotection relative to existing topical products. Other topical agents under development utilize the co-drug approach to target hyperproliferation of keratinocytes and inflammation associated with psoriasis.
Antimicrobial resistance (AMR) poses a significant threat to human, animals and the environment. Dr. Jayachandran’s primary research interest is understanding the genetic basis of antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA), a gram positive pathogen that causes nearly 11,000 deaths each year in the United States alone. Her research focuses on the role of SOS and stress (ROS, antibiotic) response in acquisition of antibiotic resistance in Staphylococcus aureus. Bacterial DNA damage stress response, also known as SOS response, includes a conserved set of genes that are induced under DNA damaging conditions. Among these are genes involved in DNA repair pathway and error-prone polymerases. The increased expression of error-prone polymerase result in increased rate of mutations, which contribute to antibiotic resistance. RecA and LexA are the main modulators of this SOS response. Two main projects in the lab are: 1) Studying the effect of RecA inhibitors on the emergence of antibiotic resistance; 2) Identifying genes that play a role in SOS and stress response using a transposon mutant library. These studies will help us understand the pathogenicity and the mechanism of antibiotic resistance in MRSA and provide insights for the development of new therapeutics.
About 70% of estrogen receptor (ER) positive breast cancers have a significantly reduced risk of invasive breast cancer through the use of various endocrine therapies. Despite the relative safety and significant anti-neoplastic and chemopreventive activities of tamoxifen and aromatase inhibitors, many initially responsive breast tumors develop resistance and ultimately recur. My current research is to investigate the secretome leading to the endocrine resistance in crosstalk between endocrine resistant breast cancer and tumor microenvironment. The long-term mission of my laboratory is to understand the steps of the endocrine resistant process in order to develop therapeutic approaches to prevent and treat endocrine resistant breast cancer effectively. The ultimate goal of my research is to bring therapies into the clinic that will improve the survival of metastatic breast cancer patients.
Dr. LaRocca’s research interest lies primarily in the mechanisms of eukaryotic programmed cell death or PCD. This includes the processes of apoptosis, necroptosis, and the molecular switches that balance the two pathways. Dr. LaRocca is particularly interested in the role of glucose in driving PCD. He is actively investigating the mechanism of hyperglycemic cell death and its role in the exacerbation of ischemic brain injury (stroke). A second project in his lab is an NIH-funded grant aimed at improving understanding of a type of red blood cell death called necroptosis and exploring ways to influence this process. Results from this work could one day lead to improved treatments for patients suffering from bacterial blood infections and other blood related disorders.
The long term research goal of Dr. Malik’s laboratory is to understand the complexities of host pathogen interactions for the development of improved prophylactics and therapeutics against important bacterial infections. She has a three-year grant by the National Institutes of Health to investigate the mechanisms by which Francisella tularensis, a category A biothreat agent survives inside the immune cells and suppresses the protective immune responses. A second area of focus is investigating the molecular mechanisms leading to the development of antibiotic resistance in methicillin resistant Staphylococcus aureus (MRSA) strains. Click the following PubMed link for additional information on research projects taking place in Dr. Malik's lab.
Dr. Musteata's research interests include the development of miniaturized analytical technology for
pharmacokinetic studies and therapeutic drug monitoring, with the purpose of creating personalized therapeutic
devices that integrate chemical analysis, decision, and drug delivery.
Work in Dr. Shah's laboratory involves structural biology. He is currently investigating genetic polymorphisms in drug metabolizing Cytochrome P450 (CYP) enzymes using structural and biophysical methods. CYP's constitute the major enzyme family in drug metabolism, and single nucleotide polymorphisms with amino acid substitutions are important contributors to interindividual variability in drug response. In brief, recombinant protein expression and purification are carried out in the laboratory in order to produce the quantities of CYP protein necessary for crystallization. The crystallographic data is collected remotely, and the three dimensional structure of the protein is then elucidated using computational tools.
Dr. Shi’s research interests are mainly focused on understanding the molecular basis of disease pathogenesis by using advanced molecular biology, virology, molecular genetics, and bioinformatics approaches. Methods used in his lab include a) HIV-1 infectious molecular clone, recombinant virus, and reporter gene technologies to study HIV phenotypes such as infection and replication; b) HIV-1 single genome amplification, sequencing and bioinformatics tools to understand genotype changes and their association with disease progression. Another major area of interest in Dr. Shi’s lab is the design and development of diagnosis assays for detecting infectious diseases, monitoring disease progression, and managing treatments.
Dr. Singh has an extensive scientific background in studying molecular mechanisms associated with HIV pathogenesis, genomic imprinting, molecular biology and mouse models of disease. Dr. Singh’s research interests include investigating the underlying molecular mechanisms involved in- i) HIV associated neurological disorder, ii) HIV latency, and iii) Viral infection induced developmental defects. Currently, Dr. Singh’s lab is focused at investigating two projects that come under NIH HIV/AIDS high priority research topics. Project 1: To investigate the consequences of HIV (Human Immunodeficiency Virus) mediated downregulation of Sonic hedgehog (Shh) signaling on brain homeostasis with specific focus on aberrant communication between astrocytes and other brain-resident cells (brain endothelial cells, pericytes, microglia and neurons). Project 2: To characterize select noncoding RNAs for their potential to establish HIV latency via- i) mediating Interferon signaling, and ii) regulating expression of HIV genome by epigenetic mechanisms. Successful completion of these studies will identify novel targets to alleviate HIV pathogenesis as well as pave the way towards HIV cure.
Research in Dr. Yager’s laboratory is focused on understanding how the body regulates inflammatory responses during flu infection. Recent studies have established a critical role for the multi-protein cytosolic NLPR3 inflammasome complex in host defense and pathophysiology during flu infection. Specifically, Dr. Yager and his team are investigating how NLRP3 inflammasome activation and resultant inflammatory cytokine secretion are regulated on a molecular level to favor host protection over immunopathology. Other areas of research include the identification of novel targets for the development of new anti-viral drugs to combat flu infection and the role of viral-induced inflammation in the etiology and pathogenesis of autism spectrum disorder.
Dr. Zheng’s research group is interested in the design and evaluation of Complex Drug Products (CDP) that are made of botanicals, peptides, and proteins from nature. Interdisciplinary technologies and translational strategies are used to ensure pharmaceutical quality, elucidate mechanisms of action, and evaluate clinical benefits and risks. These efforts can help empower regulatory decisions and enable patient-centric product design. Current projects in the lab focus on assessing the risks and benefits of medical cannabis products. This includes studying the effects of botanical and endogenous cannabinoids on the brain and the blood brain interface (BBI) as well as investigating the endocannabinoid system (ECS) on drug delivery barriers.