Texas Therapeutics Institute
Zhiqiang An, Ph.D., Professor and Director, Robert A. Welch Distinguished University Chair in Chemistry
Qingyun (Jim) Liu, Ph.D., Professor and Co-Director, Janice D. Gordon Distinguished Professor in Bowel Cancer Research
Gerald Bills, Ph.D., Professor
Ningyang Zhang, Ph.D., Associate Professor
Wenliang Li, Ph.D., Associate Professor
Kendra Carmon, PhD. Assistant Professor
Clifford Stephan, Ph.D., Assistant Professor
Kyoji Tsuchikama, Ph.D., Assistant Professor
Texas Therapeutics Institute
Texas Therapeutics Institute (TTI) at The Brown Foundation Institute of Molecular Medicine (IMM), established in 2010, is the headquarters of a consortium of the University of Texas Health Science Center Houston (UTHealth), MD Anderson and UT Austin. TTI was created to develop and commercialize medical discoveries, particularly pharmaceuticals. It is funded in part by the Texas Emerging Technology Fund.
Dr. Zhiqiang An, Professor and Director
Dr. An has an outstanding track record in the pharmaceutical industry, including the delivery of several clinical candidates of monoclonal antibodies. His current major research interest is on the mechanism of resistance to antibody treatment in breast cancer. Drug resistance is often a limiting factor for clinical efficacy of existing cancer therapies. Dr. An’s research team is studying cancer drug resistance mechanisms in the HER/ErbB signaling pathways using monoclonal antibodies as platform technology. Dr. An’s team is exploring mechanisms of cancer drug resistance and discover/develop antibodies for potential diagnostic and therapeutic applications. Dr. An is also a professor at The Graduate School of Biomedical Sciences.
Dr. Qingyun Liu, Professor and Co-Director
Dr. Liu’s group will be focused on understanding the functions of a group of receptors (LGR4, LGR5, and LGR6) that play critical roles in normal growth and development, as well as to the initiation, growth and metastasis of cancer, especially of colon cancer. We are in the process of identifying the endogenous ligands of these receptors. Our goal is to delineate the signaling mechanisms of these receptors and identify small molecule/biologicals that can modulate the activity of this system for the development of novel therapeutics in regenerative medicine and cancer treatment.
Dr. Gerald Bills, Professor
Microorganisms have produced many our most important drugs. Their hyper-biodiversity and genetic capacity for biosynthesis of organic molecules continue to yield breakthrough molecules for invention in human disease. Our research involves screening microbial natural products for therapeutic applications, making natural products through fermentation to support medicinal chemistry synthesis, and elucidating biosynthetic pathways of bioactive natural products. We seek to test the hypotheses that natural product-producing microorganisms harbor biosynthetic gene clusters and novel biosynthetic mechanisms that can be harnessed to generate new bioactive chemistry useful in intervention in infectious diseases and cancers. In parallel, we use pathway genetics and genomic manipulation in the producing organisms to aid in supplying large quantities of these natural products to support synthesis of new derivatives. Another major project tests the hypothesis that fungi adapted to living in herbivorous animal dung, an ephemeral, nutrient-rich, and competitive microbiome, can produce metabolites that interfere with cellular processes in other fungi, such as signaling pathways mediating heat stress adaptation in the invasive human pathogenic yeast Cryptococcus neoformans, or potentiate the potency of current antifungal drugs against this pathogen.
Dr. Ningyan Zhang, Associate Professor
The proteolytic process mediated by proteinases including matrix metalloproteinases (MMPs) in the tumor microenvironment plays a critical role in tumor growth, invasion, metastasis, and cancer drug resistance. Dr. Zhang and her team will study the interactions between proteinases and anti-tumor antibodies in the tumor microenvironment and will delineate the roles of proteinses (MMPs) play in tumor resistance to cancer antibody therapies.
Dr. Kendra Carmon, Assistant Professor
Dr. Carmon’s research is focused on the development of innovative antibody-drug conjugates (ADCs) to target and destroy solid tumors and cancer stem cells. During her postdoctoral training, she helped lead the discovery that R-spondin growth factors function as ligands for the stem cell receptor LGR5 to potentiate Wnt signaling. She also showed that LGR5 is continuously and rapidly internalized into the cell, making it an exceptional transit for fast and specific delivery of ADCs into target cancer cells. Based on these findings, her group is generating a series of LGR5-targeted ADCs using functionally different antibodies and distinct chemical linkers to incorporate potent cytotoxins. Recently, they showed that anti-LGR5 ADCs can effectively eradicate colon tumors and prevent recurrence in xenograft mouse models. Current research is also focused on investigating the role of LGR5 in cancer and drug resistance. The goal of this work is to provide proof-of-concept for the future development of novel target-based ADCs for cancer therapy.
Dr. Wenliang Li, Assistant Professor
Dr. Li’s lab is interested in studying cancer metastasis that is responsible for over 90% of cancer death. Much of their work involves in functionally exploring human kinome (kinases) in vitro and in vivo, to identify new players in cancer metastasis, as an avenue to gain novel insights into the still elusive mechanisms of metastasis. The goal of their studies is to discover new prognostic markers, drug targets and better therapeutics for human metastatic diseases.
Dr. Clifford Stephan, Assistant Professor
Dr. Stephan received his Ph.D. from the Department of Pharmacology at Vanderbilt University, Nashville, Tennessee. He is a vascular biologist with extensive experience in pharmacology and drug discovery. Dr. Stephan began his biotechnology/pharmaceutical career at Encysive Pharmaceuticals, Houston, Texas in 1993. He started and ran the High Throughput Screening New Drug Discovery Program at Encysive, becoming its Director in 2005. Since 2007 he has served as the Director of the John S Dunn high-throughput and high-content screening core laboratory of the Gulf Coast Consortium (GCC) for Chemical Genomics and is responsible for all screening campaigns, data acquisition, analysis and database management. Beginning in 2011, Dr. Stephan will serve as the Principle Investigator for the Cancer Prevention Research in Texas (CPRIT) GCC High-Throughput Screening Program concentrating on development of drug combinations for use in cancer prevention, overcoming resistance or decreasing overall toxicity. Dr. Stephan lectures regularly on drug discovery in graduate programs and has organized GCC workshops on high–throughput screening and its application to drug discovery research.
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