Ian Macara, Ph.D.
Stephen W. Fesik, Ph.D.
Signal Transduction and Chemical Biology
The Signal Transduction and Chemical Biology Research Program (ST) is an active group of basic, translational, and clinical scientists whose goal is to understand how signaling networks control cell proliferation and function, to identify drug leads, and to develop new cancer therapeutics.
The program is organized into four groups with common interests:
Stem Cell Biology
Cell Cycle Control
The ST program currently has 42 members from over a dozen departments and centers within Vanderbilt University and Meharry, including both basic science and clinical departments. Our activities are aimed at two broadly defined objectives:
To promote outstanding basic research in the area of signaling networks, developing the strongest possible foundation of fundamental knowledge and new technology
To encourage and cultivate translational cancer research, through drug discovery, clinical trials, and by selective funding of pilot projects and other avenues to promote collaborations between outstanding basic and clinical research groups at Vanderbilt
Based on these goals, the formal aims for the program are:
To increase awareness of the research going on within each member’s laboratory and thereby encourage collaborative interactions within the program (intraprogrammatic) and with other VICC programs (interprogrammatic)
To aggressively cultivate the cutting-edge basic science and technology expertise required to foster and promote effective translational research within the Cancer Center
Ian Macara, Ph.D. has conducted highly innovative research in cancer biology for several decades, and on cell polarity mechanisms for over 10 years. Early in his career he discovered that tyrosine kinases associate with a phosphatidyl inositol kinase (PNAS 1984) – which led to the identification by others of PI3K; and he identified the first known Ras exchange factor (Science 1990). He also identified a role for RanGTP in nuclear export (Science 1997), and demonstrated a role for histones in docking of the Ran exchange factor to chromatin (Science 2001).
In the field of cell polarity, he discovered that the mammalian Par proteins, Par3, Par6, and aPKC form a complex with the Cdc42 GTPase (Nat. Cell Biol, 2000), and with the Pals1/Crumbs3 polarity complex (Nat Cell Biol 2003). He also discovered that the Pins/LGN protein interacts with NuMA to control astral microtubules association with the cell cortex so as to determine spindle pole orientation during mitosis (Nat Cell Biol, 2001; Cell 2004). This important mechanism was subsequently found to be conserved in Drosophila and C. elegans. The mechanism by which Pins/LGN is excluded from the apical surface of epithelial cells (Curr. Biol, 2010) was also recently confirmed in Drosophila. He also elucidated the signaling pathways downstream of the Par3 and Par6 polarity proteins both in epithelial cells and in neurons (Nat. Cell Biol, 2005 and 2006; Dev Cell 2008).
More recently, he has developed methods using lentiviral transduction and stem cell transplantation to study gene function in mammary gland development (Genes & Dev 2009) and was awarded a 3-year Komen grant in 2007 (with Dr. Lannigan as co-PI) to develop a new human breastoid ex vivo 3D culture model that can be employed for studies of primary human breast tumors (Genes & Dev 2011). In other work, he discovered the long-sought enzyme that methylates the -amino group at the N-terminus of multiple proteins (Nature 2010), performed the first genome-wide screen for localized RNAs in mammalian cells (Nature 2008), and discovered an unexpected link between septins and DNA damage responses (Cell 2007). Importantly, his laboratory recently identified a role for polarity proteins as suppressors of breast tumor growth and metastasis (Cancer Cell, 2012). A major goal of the laboratory is to tackle fundamental questions about the role of the cell polarity machinery in breast cancer initiation and dissemination, employing biologically-relevant mouse and human models. He has published over 170 research papers, has an h-index of 62, and is placed in the top 5% of cited authors for journals in Biology and Biochemistry (per analysis by Thomson Reuters).
The research in Dr. Macara’s laboratory is currently supported by 3 NIH RO1 grants (CA 132898, GM 070902, and GM50526), and by a Susan Komen Breast Cancer Foundation grant (IIR12223770) on the identification of driver mutations in TNBC using primary 3D organoids.
Dr. Macara has trained over 25 graduate students and 30 postdoctoral fellows, many of whom have gone on to academic positions. Recently, from his laboratory Dr. McCaffrey became an assistant professor in the Cancer Center at McGill University; Dr. Mili joined the faculty in the NCI; Dr. Tooley became an assistant professor at Louisville University; and Dr. Zhang took an assistant professorship at Rutgers University.
Stephen W. Fesik, Ph.D. is the Orrin H. Ingram, II Chair in Cancer Research and a Professor of Biochemistry, Pharmacology, and Chemistry in Vanderbilt University School of Medicine. He is also a member of the Vanderbilt Ingram Cancer Center (VICC), the Vanderbilt Institute of Chemical Biology (VICB) and the Center for Structural Biology (CSB).
The focus of his research is on cancer drug discovery using fragment-based approaches and structure-based drug design. Prior to joining Vanderbilt in May, 2009, Dr. Fesik was the Divisional Vice President of Cancer Research at Abbott (2000-2009) where he built a pipeline of compounds that are showing promising anti-cancer activities in early stage clinical trials. In addition, while he was at Abbott, he developed several new NMR methods, determined the three-dimensional structures of several proteins and protein/ligand complexes, pioneered a method for drug discovery called SAR by NMR, and applied this method to identify and optimize ligands for binding to many protein drug targets.
His research has also involved the use of siRNA for target identification and target validation. Dr. Fesik has published more than 240 papers, trained 36 postdoctoral fellows, has been a reviewer for the NIH Biophysical Chemistry Study Section, and has served as a member of the Editorial Boards of the Journal of Medicinal Chemistry, Journal of Biomolecular NMR, Biophysical Journal, Molecular Cell, Chemical Biology & Drug Design, ChemMedChem, Molecular Cancer Therapeutics, Oncogene, Combinatorial Chemistry and High Throughput Screening, and the Highlights Advisory Panel for Nature Reviews Cancer. He has served on the Keystone Scientific Advisory Board and Board of Directors and currently is a member of the Scientific Advisory Board of the UPenn Abramson Cancer Center, Aileron Therapeutics, and the Bruker Board of Directors. He has obtained several awards, including the Chairman’s Award (1996), Outstanding Researcher of the Year Award (1997) , and the Researcher of the Year Team Award (2008) from Abbott, the Servier Lecturer Award (1998) from the University of Montreal, the ASBMB-Fritz Lipmann Lectureship Award (1999), the Lifetime Achievement Award in Nuclear Magnetic Resonance from EAS (2003), the SBS Technology Innovation Award (2010), and the NIH Director's Pioneer Award (2010). Recently he has been elected Fellow of the American Association for the Advancement of Science (AAAS).
- Adunyah, Samuel E., Ph.D.
Professor and Chair of Cancer Biology, Meharry Medical College; Researcher
- Andl, Thomas, Ph.D.
Assistant Professor of Medicine (Dermatology); Researcher
- Brandt, Stephen J., M.D.
Professor of Medicine (Hematology/Oncology); Professor of Cell and Developmental Biology; Professor of Cancer Biology; Researcher
- Brash, Alan R., Ph.D.
Professor of Pharmacology; Researcher
- Breyer, Richard M., Ph.D.
Ruth King Scoville Professor of Medicine (Nephrology) ; Researcher
- Brown, H. Alex, Ph.D.
Bixler-Johnson-Mayes Professor of Pharmacology; Researcher
- Burnette, Dylan, Ph.D.
Assistant Professor of Cell and Developmental Biology
- Carter, Bruce D., Ph.D.
Professor of Biochemistry; Associate Director for Education and Training, Vanderbilt Brain Institute; Investigator, Kennedy Center for Research & Humanities; Director of Graduate Studies in Neuroscience; Researcher
- Chen, Zhenbang, Ph.D.
Associate Professor; Researcher
- Chiang, Chin, Ph.D.
Professor of Cell and Developmental Biology; Researcher
- Colbran, Roger J., Ph.D.
Professor of Molecular Physiology and Biophysics; Researcher
- Cooper, Michael K., M.D.
Associate Professor of Neurology; Researcher
- Davé, Utpal P., M.D.
Assistant Professor of Medicine (Hematology/Oncology); Assistant Professor of Cancer Biology; Hematologist/Oncologist
- de Caestecker, Mark P., M.D., Ph.D.
Assistant Professor of Medicine (Nephrology); Researcher
- Fesik, Stephen W., Ph.D.
Co-Leader, Signal Transduction and Chemical Biology Research Program; Orrin H. Ingram, II Professor of Cancer Research; Professor of Biochemistry, Pharmacology and Chemistry; Researcher
- Hamid, Rizwan, M.D., Ph.D.
Associate Professor of Pediatrics; Assistant Professor of Cancer Biology; Researcher
- Hann, Stephen R., Ph.D.
Professor of Cell and Developmental Biology; Researcher
- Hawiger, Jack Jacek, M.D., Ph.D.
Distinguished Professor of Medicine (Allergy, Pulmonary, and Critical Care); Louise B. McGavock Endowed Chair; Professor of Physiology and Molecular Biophysics; Researcher
- Hiebert, Scott W., Ph.D.
Associate Director for Basic Science Research and Shared Resources; Hortense B. Ingram Professor of Cancer Research; Professor of Biochemistry; Associate Professor of Medicine; Researcher
- Ihrie, Rebecca A., Ph.D.
Assistant Professor of Cancer Biology; Assistant Professor of Neurological Surgery
- Irish, Jonathan M., Ph.D.
Assistant Professor of Cancer Biology; Assistant Professor of Pathology, Microbiology and Immunology
- Lau, Ken S, Ph.D.
- Lee, Ethan, M.D., Ph.D.
Associate Professor of Cell and Developmental Biology; Associate Professor of Pharmacology; Researcher
- Liebler, Daniel C., Ph.D.
Director, Jim Ayers Institute for Precancer Detection and Diagnosis; Ingram Professor of Cancer Research; Professor of Biochemistry, Pharmacology, and Biomedical Informatics; Director, Center in Molecular Toxicology; Researcher
- Lindsley, Craig W., Ph.D.
William K. Warren, Jr. Professor of Medicine; Professor of Pharmacology, Chemistry; Researcher
- Link, Andrew J., Ph.D.
Associate Professor of Pathology, Microbiology and Immunology; Assistant Professor of Biochemistry; Researcher
- Lopez, Carlos F., Ph.D.
Assistant Professor of Cancer Biology; Assistant Professor of Bioengineering (adjunct); Assistant Professor of Biomedical Informatics (adjunct); Researcher
- Macara, Ian, Ph.D.
Co-Leader, Signal Transduction and Chemical Biology Research Program; Louise B. McGavock Professor and Chair of Cell and Developmental Biology; Researcher
- MacGurn, Jason Andrew, Ph.D.
- Magnuson, Mark A., M.D.
Louise B. McGavock Professor of Molecular Physiology and Biophysics; Medicine, Cell and Developmental Biology; Director, Center for Stem Cell Biology; Researcher
- Marnett, Lawrence J., Ph.D.
Mary Geddes Stahlman Professor of Cancer Research; University Professor of Biochemistry and Chemistry; Professor of Pharmacology; Director, Vanderbilt Institute of Chemical Biology; Director, A.B. Hancock Jr. Memorial Laboratory; Director, Vanderbilt Institute; Researcher
- Matusik, Robert J., Ph.D.
William L. Bray Professor of Urologic Surgery; Professor of Cell & Developmental Biology, Cancer Biology; Director of Urologic Surgery Research; Researcher
- Neuert, Gregor, Ph.D.
- Stein, Roland W., Ph.D.
Mark Collie Chair in Diabetes Resesarch; Professor of Molecular Physiology and Biophysics, Cell and Developmental Biology; Researcher
- Stewart, LaMonica V., Ph.D.
Associate Professor of Biochemistry and Cancer Biology, Meharry Medical College; Researcher
- Sulikowski, Gary , Ph.D.
Professor of Chemistry; Director, Chemical Synthesis Core
- Tabb, David L., Ph.D.
Associate Professor of Biochemistry, Biomedical Informatics ; Mass Spectrometry Bioinformaticist
- Wang, Jialiang, Ph.D.
Assistant Professor of Cancer Biology; Assistant Professor of Neurological Surgery; Director, Neurosurgical Oncology Laboratory
- Waterson, Alex G., Ph.D.
Research Assistant Professor of Pharmacology, Chemistry; Researcher
- Weil, P. Anthony, Ph.D.
Professor of Molecular Physiology & Biophysics; Researcher
- Wente, Susan R., Ph.D.
Provost; Vice Chancellor for Academic Affairs; Professor of Cell and Developmental Biology ; Researcher