Mohamed Trebak, PhD

Professor

E1355 Thomas E. Starzl Biomedical Science Tower
Pittsburgh, PA 15231
Phone: 412-648-1381
Fax: 412-648-1945

Education

B.Sc. (Plant Physiology),  Université de Rabat, Morocco, 1991
M.Sc. (Biochemistry), Université de Liège, Belgium, 1994
Ph.D (Biochemistry), Université de Liège, Belgium, 1998
NIH postdoctoral Fellow, Wistar Institute, Philadelphia, PA, 1999-2000
IRTA postdoctoral Fellow, NIEHS/NIH, Research Triangle Park, NC, 2001-2006

 
Mohamed Trebak, PhD
We use biochemical, biophysical and imaging techniques to understand the signalling mechanisms of native Ca2+ permeable channels in a variety of cell systems, including a number of cancer cells, astrocytes, lymphocytes, vascular and airway smooth muscle cells and endothelial cells. We are particularly interested in two classes of ion channels: the transient receptor potential canonical (TRPC) channels and the components of the store-operated calcium entry (SOCE) pathway, STIM and Orai proteins as they pertain to cell proliferation, migration, growth, survival and invasion. We use animal models of disease as well as knockout mice that are exclusively deficient for a single ion channel molecule in a specific tissue and transgenic mice. Current projects include:
 
Mechanisms of receptor evoked cytosolic Ca2+ oscillations in non-excitable cells and the role of native STIM, Orai and IP3 receptors in shaping the cytosolic Ca2+ microdomains that control the activation of nuclear factor for activated T cells (NFAT) transcription factors isoforms.

The role of the mitochondrial Ca2+ uniporter (MCU) and the Na+/Ca2+ exchanger (NCLX) in transcriptional programs that control cell growth, metabolism, and invasion of colorectal cancer.

Control of transcriptional and metabolic reprogramming of smooth muscle remodeling in hypertension and asthma by Ca2+ signals through CRAC channels.

Regulation of brown adipose tissue function, thermogenesis, and obesity by Orai3-mediated Ca2+ signaling.

Molecular make-up of CRAC channels in B lymphocytes and contribution of Orai isoforms to B cell activation, antibody production and humoral immunity.

Interorganellar Ca2+ transfer between cytosol-mitochondria-endoplasmic reticulum and role in cellular bioenergetics, mitochondrial dynamics, and transcriptional regulation.

Journal Articles

Emrich SM, Yoast RE, Zhang X, Xin P, Johnson MT, Hempel N, Gill DL, Sneyd J, Yule DI and Trebak M. 2021. Omnitemporal choreographies of all five STIM/Orai and IP3Rs underlie the complexity of mammalian Ca2+ signaling. Cell Reports. 34(9):108760.
 
Yoast RE, Emrich SM, Zhang X, Xin P, Johnson MT, Fike AJ, Walter V, Hempel N, Yule DI, Sneyd J, Gill DL and Trebak M. 2020. The Native ORAI Channel Trio Underlies the Diversity of Ca2+ Signaling Events. Nature Communications. 11(1):2444.
 
Johnson MT, Gudlur A, Zhang X, Xin P, Emrich SM, Yoast RE, Courjaret R, Nwokonko R, Li W, Machaca K, Gill DL, Hogan PG and Trebak M. 2020. L-type Ca2+ Channel Blockers Promote Vascular Remodeling through Activation of STIM Proteins. Proc. Natl. Acad.Sci. USA. 117(29):17369-17380.
 
Pathak T, Gueguinou M, Walter V, Delierneux C, Johnson MT, Zhang X, Xin P, Yoast RE, Emrich SM, Yochum GS, Sekler I, Koltun WA, Gill DL, Hempel N and Trebak M. 2020. Dichotomous role of the human mitochondrial Na +/Ca 2+/Li + exchanger NCLX in colorectal cancer growth and metastasis. eLife. 9:e59686.
 
Emrich SM, Yoast RE, Xin P, Zhang X, Pathak T, Nwokonko R, Gueguinou MF, Subedi KP, Zhou Y, Ambudkar IS, Hempel N, Machaca K, Gill DL and Trebak M. 2019. Crosstalk between STIM2 N-terminal and C-terminal Domains Determines Enhanced STIM2 Sensitivity. J. Biol. Chem. 294(16):6318-6332.
 
Ben-Kasus Nissim T, Zhang X, Elazar A, Roy S, Stolwijk JA, Zhou Y, Motiani RK, Gueguinou M, Hempel N, Hershfinkel M, Gill DL, Trebak M* and Sekler I*. 2017. Mitochondria control store-operated Ca2+ entry through Na+ and redox signals. EMBO J. 36:797-815. *Senior authors.
 
Desai PN, Zhang X, Wu S, Putney JW and  Trebak M. 2015. Specific requirement for Orai1α in store-independent Orai1/Orai3 Ca2+ currents. Science Signaling. 8(387): ra74.