mTOR: Mammalian TOR (mTOR) is an evolutionarily conserved serine/threonine kinase that integrates signals from growth factors, nutrients, and stresses to regulate multiple processes, including mRNA translation, cell-cycle progression, autophagy, and cell survival. Several lines of evidence suggest that increased signaling of the mTOR pathway is involved in tumor formation
By using genetic approaches in both cell culture and animal models, my research goals are to understand and identify:
* What are new components or targets of mTOR signaling network?
* What are the functions of the components in the mTOR signaling network?
* How do these functions might be altered or involved in metabolic diseases and cancer?
* How do cells manage the regulation of mTOR pathway under certain conditions?
P53: Cancer is a genetic disorder caused by mutations in genes critically involved in the control of cell proliferation. Long-lived organisms, such as humans, have evolved strategies to restrict the development of potentially malignant cells. The p53 family of tumor suppressor genes (Fig. 2) provides important defense against cancer.
Activated in response to DNA damage and to oncogenic signaling the three proteins of this family - p53, p63 and p73 - cooperate to induce apoptosis and thus restrict tumor formation by eliminating potentially malignant cells. Importantly, alteration of this coordination often causes cancer.
Taken together, despite the striking similarities among the p53 family members, however, their roles in tumorigenesis appear to be quite different.
My research focuses on a comparative analysis of the three genes using genetic approaches in both cell culture and animal models to understand:
* How do p53 and its family members suppress tumorigenesis?
* How do the p53 family inhibitors dNp73 and dNp63 enhance tumor formation?
* How do the p53 family members regulate gene expression?
* How do the p53 family members interact with other signaling networks?
* What is the function of the p53 family members in normal development?
Cam M, Bid HK, Xiao L, Zambetti GP, Houghton PJ, Cam H. 2014. p53/TAp63 and AKT Regulate mTORC1 Signaling through two Independent Parallel Pathways in the Presence of DNA Damage. J Biol Chem. Vol. 289, no. 7. (February): 4083-94.
Bid HK, Roberts RD, Cam M, Audino A, Kurmasheva RT, Lin J, Houghton PJ, Cam H. 2014. ?Np63 promotes pediatric neuroblastoma and osteosarcoma by regulating tumor angiogenesis. Cancer Res. Vol. 74, no. 1. (January): 320-9.
Shen C, Oswald D, Phelps D, Cam H, Pelloski CE, Pang Q, Houghton PJ. 2013. Regulation of FANCD2 by the mTOR pathway contributes to the resistance of cancer cells to DNA double-strand breaks. Cancer Res. Vol. 73, no. 11. (June): 3393-401.
Cam,Hakan; Houghton,Peter,J. 2011. Regulation of mammalian target of rapamycin complex 1 (mTORC1) by hypoxia: causes and consequences. TARGETED ONCOLOGY. Vol. 6, no. 2. (June): 95-102.
Cam,Hakan; Easton,John,B; High,Anthony; Houghton,Peter,J. 2010. mTORC1 Signaling under Hypoxic Conditions Is Controlled by ATM-Dependent Phosphorylation of HIF-1 alpha. MOLECULAR CELL. Vol. 40, no. 4. (November): 509-520.
Cam H, Easton JB, High A, Houghton PJ. mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1α. Mol Cell. 2010 Nov 24;40(4):509-20. PubMed ID: 21095582
Cam,H; Houghton,PJ. 2008. mTOR: A critical regulator of p53 during a variety of stresses. CELLSCIENCE. Vol. 4, no. 3. (January): ISSN: 1742-8130.
Cam H, Houghton PJ. mTOR: a critical regulator of p53 during a variety of stresses. Cellscience. 2008 Jan; Vol. 4 No 3 ISSN 1742-8130
Cam,Hakan; Griesmann,Heidi; Beitzinger,Michaela; Hofmann,Lars; Beinoraviciute-Kellner,Rasa; Sauer,Markus; Huettinger-Kirchhof,Nicole; Oswald,Claudia; Friedl,Peter; Gattenloehner,Stefan; Burek,Christof; Rosenwald,Andreas; Stiewe,Thorsten. 2006. p53 family members in myogenic differentiation and rhabdomyosarcoma development. CANCER CELL. Vol. 10, no. 4. (October): 281-293.
Huttinger-Kirchhof,N; Cam,H; Griesmann,H; Hofmann,L; Beitzinger,M; Stiewe,T. 2006. The p53 family inhibitor Delta Np73 interferes with multiple developmental programs. CELL DEATH AND DIFFERENTIATION. Vol. 13, no. 1. (January): 174-177.
Cam H, Griesmann H, Beitzinger M, Hofmann L, Beinoraviciute-Kellner R, Sauer M,Hüttinger-Kirchhof N, Oswald C, Friedl P, Gattenlöhner S, Burek C, Rosenwald A, Stiewe T. p53 family members in muscle differentiation and rhabdomyosarcoma development. Cancer Cell. 2006 Oct;10(4):281-93. PubMed ID: 17045206
Huttinger-Kirchhof N, Cam H, Griesmann H, Hofmann L, Beitzinger M, Stiewe T.The p53 family inhibitor δNp73 interferes with multiple developmental
programs. Cell Death Differ. 2006 Jan;13(1):174-7. PubMed ID: 16341031
Engels,B; Cam,H; Schuler,T; Indraccolo,S; Gladow,M; Baum,C; Blankenstein,T; Uckert,W. 2003. Retroviral vectors for high-level transgene expression in T lymphocytes. HUMAN GENE THERAPY. Vol. 14, no. 12. (August): 1155-1168.
Engels B, Cam H, Schuler T, Indraccolo S, Gladow M, Baum C, Blankenstein T, Uckert W.Retroviral vectors for high-level transgene expression in T lymphocytes. Human Gene Ther. 2003 Aug 10;14(12):1155-68. PubMed ID: 12908967