One major goal of my group is to obtain mechanistic understanding of growth factor signaling, and the implications of these findings to aberrant cell functions in the setting of different diseases. Specifically, we are studying mitogenic signaling pathways that are regulated by small GTPases of the Rho family and their upstream activators, guanine nucleotide exchange factors (GEFs) from the Dbl family, which mediate and control signaling information flow from cell surface receptors to the intracellular machinery. In this area, we focused our efforts on both the GTPases themselves and their upstream GEFs, and their actions in normal and malignant settings. In addition, we devote a major research effort to the roles and molecular mechanisms that regulate reactive oxygen species in the context of human health and disease, and the impact of antioxidants (e.g. vitamin E) levels in the context of pathologies such as neurodegeneration, cancer, and metabolic perturbations. Our approach in attacking both of these fundamental questions is highly interdisciplinary and relies on diverse experimental approaches, including molecular and cell biology, biophysics, synthetic chemistry, and high-resolution microscopy. In addition, our work has important translational aspects in that we examine the relevance of our findings to human disease through collaborations with epidemiologists, geneticists and clinicians.
I focus on signal transduction pathways that regulate normal cell growth and are disrupted by oncogenic mutations. In addition, I research molecular mechanisms underlying cancer chemo-preventative agents such as vitamin E.
- NIH/NCI R21 CA254968
- Understanding and Targeting Tiam1 in Cancer.
- 07/01/2021 - 06/30/2023.
- Role: PI
- NIH/NIDDK R01 DK125115
- Functions of vitamin E and the tocopherol transfer protein
- 04/01/2021 - 03/31/2026
- Role: PI
- Editorial Board, Free Radicals in Biology and Medicine
- Editorial Board, Biofactors
- Editorial Board, J. Cell Signaling
- Special Issue editor, Nutrients
- Editorial board, Vitamins and Minerals
Vitamin E sequestration by liver fat in humans. JCI Insight. 2020 Jan 16;5(1). doi: 10.1172/jci.insight.133309. PubMed PMID: 31821172; PubMed Central PMCID: PMC7030816.
Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein. J Biol Chem. 2016 Aug 12;291(33):17028-39. doi: 10.1074/jbc.M116.734210. Epub 2016 Jun 15. PubMed PMID: 27307040; PubMed Central PMCID: PMC5016108.
Vitamin E and neurodegeneration. Neurobiol Dis. 2015 Dec;84:78-83. doi: 10.1016/j.nbd.2015.04.002. Epub 2015 Apr 22.
Tyrosine phosphorylation of Dbl regulates GTPase signaling. J Biol Chem. 2014 Jun 13;289(24):17195-202. doi: 10.1074/jbc.M114.573782. Epub 2014 Apr 28. PubMed PMID: 24778185; PubMed Central PMCID: PMC4059160.
- Chung et al. Dynamic regulation of hepatic vitamin E secretion by the α-tocopherol transfer protein. Annual Experimental Biology Meeting, March 28 – April 1, 2015, Boston, MA
- Chung et al. Vitamin E and phosphatidyl inositol phosphates drive hepatic alpha-tocopherol transfer protein localization. Annual meeting of the Society for Free Radical Biology and Medicine, November 18-22, 2015, Boston, MA
- Ulatowski et al. Regulation of Tiam1-mediated invasion by tyrosine phosphorylation. FASEB Science Research Conference on Regulation and Function of Small GTPases. June 7-12, 2015, West Palm Beach, FL
- Ulatowski et al. Vitamin E protects against PUFA-induced behavioral and motor deficits. Annual Experimental Biology meeting, April 26-30, 2014, San Diago, CA
- Thakur et al. The alpha-tocopherol transfer protein (TTP) regulates Vitamin E transport across placental cell monolayers. Annual Experimental Biology meeting, April 26-30, 2014, San Diago, CA
- Chung et al. Dynamic regulation of hepatic vitamin E secretion by the α-tocopherol transfer protein. Annual Experimental Biology meeting, April 26-30, 2014, San Diago, CA
- Thakur et al. Vitamin E and nonalcoholic fatty liver disease (NAFLD). Annual Experimental Biology meeting, April 20-24, 2013, Boston, MA. (FASEB J April 9, 2013 27:1017.11)
- Chung et al. Dynamic regulation of hepatic vitamin E secretion by the α-tocopherol transfer protein. Annual Experimental Biology meeting, April 20-24, 2013, Boston, MA. (FASEB J April 9, 2013 27:373.1)
- Ulatowski et al. Alpha-TTP-expressing astrocytes regulate α-tocopherol homeostasis in the CNS. Annual Experimental Biology meeting, April 20-24, 2013, Boston, MA. (FASEB J April 9, 2013 27:814.2)
- Ulatowski et al. Behavioral Manifestations of oxidative stress. Annual meeting of the Society of Free Radicals in Biology and Medicine, November 20-24, San Antonio, Texas.
- Committee on Appointments, Promotions and Tenure, CWRU School of Medicine
- Committee on Budget, Finance, and Compensation, CWRU School of Medicine
- Bylaws Committee, CWRU School of Medicine