Shawn B. Bratton, Ph.D.
Department of Epigenetics and Molecular Carcinogenesis, Division of Division of Discovery Science
Present Title & Affiliation
Primary Appointment
Associate Professor, Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX
Dual/Joint/Adjunct Appointment
Associate Professor, Department of Division of Pharmacology and Toxicology, Division of College of Pharmacy, The University of Texas at Austin, Austin, TX
Research Interests
In the Bratton laboratory, we are primarily interested in two basic areas of research: apoptosis (programmed cell death) and autophagy (self-cannibalism). Apoptosis is critical for normal development in multicellular organisms from flies to humans, and it works in concert with cell division to maintain the normal size and function of adult tissues. Diseases associated with increased rates of apoptosis include neurodegenerative disorders (Alzheimer's Disease and Parkinson's Disease), AIDS, myelodysplastic syndromes, and ischemic injury (stroke and myocardial infarction), whereas those associated with inhibition of apoptosis include autoimmune diseases and cancer. In fact, defective apoptosis is a hallmark of cancer and a major cause of resistance during cancer therapy. Autophagy, on the other hand, is primarily a cell survival rather than a cell death process. In cells deprived of growth factors or nutrients, intracellular proteins and even entire organelles are broken down and proteolytically digested within lysosomes in order to provide energy and macromolecules for essential biosynthetic pathways. Autophagy therefore plays an important role during tumorigenesis, as it allows early solid tumors to survive prior to vascularization (angiogenesis), and it promotes chemoresistance by allowing tumor cells to remove damaged proteins and organelles. Finally, emerging evidence suggests that cross-talk exists between apoptotic and autophagic pathways, in that established regulators of apoptosis, such as the tumor suppressor p53 and antiapoptotic Bcl-2 family members, also regulate autophagy.
Education & Training
Degree-Granting Education
| 1999 | The University of Texas at Austin, Austin, TX, USA, PHD, Pharmacology and Toxicology |
| 1992 | The University of Texas Medical Branch, Galveston, TX, USA, BS, Medical Technology |
| 1991 | The University of Texas at Austin, Austin, TX, USA, BS, Molecular Biology |
Postgraduate Training
| 1999-2001 | Research Fellowship, Medical Research Council Toxicology Unit, Medical Research Council Toxicology Unit, Leicester |
Selected Publications
Peer-Reviewed Articles
- Wu CC, Lee S, Malladi S, Chen MD, Mastrandrea NJ, Zhang Z, Bratton SB. The Apaf-1 apoptosome induces formation of caspase-9 homo- and heterodimers with distinct activities. Nat Commun 7:13565, 2016. e-Pub 2016. PMID: 27882936.
- Richburg JH, Myers JL, Bratton SB. The role of E3 ligases in the ubiquitin-dependent regulation of spermatogenesis. Semin Cell Dev Biol 30:27-35, 2014. e-Pub 2014. PMID: 24632385.
- Mahajan IM, Chen MD, Muro I, Robertson JD, Wright CW, Bratton SB. BH-3-only protein BIM mediates heat shock-induced apoptosis. PLoS One 9(1):e84388, 2014. e-Pub 2014. PMID: 24427286.
- Yeh TC, Bratton SB. DrICE resurrects Grim to antagonize DIAP1. Cell Cycle 13(5):685-6, 2014. e-Pub 2014. PMID: 24526123.
- Wu CC, Bratton SB. Regulation of the Intrinsic Apoptosis Pathway by Reactive Oxygen Species. Antioxid Redox Signal 19(6):546-58, 2013. e-Pub 2012. PMID: 22978471.
- Yeh TC, Bratton SB. Caspase-dependent regulation of the ubiquitin-proteasome system through direct substrate targeting. Proc Natl Acad Sci U S A 110(35):14284-9, 2013. e-Pub 2013. PMID: 23940367.
- Bratton SB, Salvesen GS. Regulation of the Apaf-1-caspase-9 apoptosome. J Cell Sci 123(Pt 19):3209-14, 2010. PMID: 20844150.
- Son JK, Varadarajan S, Bratton SB. TRAIL-activated stress kinases suppress apoptosis through transcriptional upregulation of MCL-1. Cell Death Differ 17(8):1288-301, 2010. e-Pub 2010. PMID: 20168333.
- Malladi S, Challa-Malladi M, Fearnhead HO, Bratton SB. The Apaf-1*procaspase-9 apoptosome complex functions as a proteolytic-based molecular timer. EMBO J 28(13):1916-25, 2009. e-Pub 2009. PMID: 19494828.
- Choi YE, Butterworth M, Malladi S, Duckett CS, Cohen GM, Bratton SB. The E3 ubiquitin ligase cIAP1 binds and ubiquitinates caspase-3 and -7 via unique mechanisms at distinct steps in their processing. J Biol Chem 284(19):12772-82, 2009. e-Pub 2009. PMID: 19258326.
- Challa M, Malladi S, Pellock BJ, Dresnek D, Varadarajan S, Yin YW, White K, Bratton SB. Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease. EMBO J 26(13):3144-56, 2007. e-Pub 2007. PMID: 17557079.
- Chandra D, Bratton SB, Person MD, Tian Y, Martin AG, Ayres M, Fearnhead HO, Gandhi V, Tang DG. Intracellular nucleotides act as critical prosurvival factors by binding to cytochrome C and inhibiting apoptosome. Cell 125(7):1333-46, 2006. PMID: 16814719.
Invited Articles
- Wible DJ, Bratton SB. Reciprocity in ROS and autophagic signaling. Curr Opin Toxicol 7:28-36, 2018. e-Pub 2017. PMID: 29457143.
- Wu CC, Bratton SB. Caspase-9 swings both ways in the apoptosome. Mol Cell Oncol 4(2):e1281865, 2017. e-Pub 2017. PMID: 28401186.
Patient Reviews
CV information above last modified April 15, 2024