Dr. Felipe Samaniego
The University of Texas MD Anderson Cancer Center
Departments of Lymphoma/Myeloma & Clinical Cancer Prevention
- Regulation of death receptors in cancer therapy
Almost all of the 60,000 cases of lymphoma occurring annually in the United States have no known etiology, and nearly half of those diagnosed with these cancers will die of the disease. Although we know that cell death (apoptosis) is key to developing therapies, advances in treatment strategies have been hampered by minimal understanding of the defective regulation of cancer cell death.
Our research team in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center is studying how to efficiently kill lymphoma and blood cancer cells. Cells normally undergo suicide after death receptors Fas and TRAIL are switched on. But in cancer cells, this switch is defective, and cells do not die. We discovered that the cancer-causing human herpesvirus-8 K1 protein binds Fas and blocks the Fas death receptor so that cells do not die. Likewise, we have also identified CD74 and nucleolin, cellular death receptor inhibitors that are highly expressed in cancer cells and block cell death. We have also identified promyelocytic leukemia (PML protein and the recombinant cancer-causing protein promyelocytic leukemia protein-retinoic acid receptor alpha (PML/RAR) as, respectively, facilitating and blocking Fas-mediated apoptosis.
To improve cancer therapy by facilitating cancer death, we plan to show how these inhibitors block cancer cell death and investigate how to block these inhibitors. We will investigate how the inhibitors bind Fas and design short proteins that compete with that binding in order to facilitate cell death. We will test the short proteins in mice to show whether they block the inhibitor, causing cell death. These experiments will serve as the basis for developing anticancer drugs and testing them in clinical trials with patients who lack effective therapies. Support for our research is provided by grants from various agencies, fellowships, and gifts from the many grateful patients treated at MD Anderson. A prospective graduate student in this laboratory will work closely with a group of post-doctoral fellows, technicians, and faculty mentors on a project to investigate how to regulate death receptors with the goal of applying these findings to the development of cancer therapies. We have a vast number of resources available to assist students in their projects, including recombinant DNA reagents, mice tumor models, access to tumor banks, and ongoing clinical trials for clinical investigation of new therapies.
Younes A, Pro B, Robertson MJ, Flinn IW, Romaguera JE, Hagemeister F, Dang NH, Fiumara P, Loyer EM, Cabanillas FF, McLaughlin PW, Rodriguez MA, Samaniego F. Phase II clinical trial of interleukin-12 in patients with relapsed and refractory non-Hodgkin's lymphoma and Hodgkin's disease. Clin Cancer Res 10(16):5432-8, 2004. PMID: 15328181.
Prakash O, Swamy OR, Peng X, Tang ZY, Li L, Larson JE, Cohen JC, Gill J, Farr G, Wang S, Samaniego F. Activation of Src kinase Lyn by the Kaposi sarcoma-associated herpesvirus K1 protein: implications for lymphomagenesis. Blood 105(10):3987-94, 2005.
Wang S, Wang S, Maeng H, Young DP, Prakash O, Fayad LE, Younes A, Samaniego F. K1 protein of human herpesvirus 8 suppresses lymphoma cell Fas-mediated apoptosis. Blood 109(5):2174-82, 2007. PMID: 1801039.
Berkova Z, Tao RH, Samaniego F. Milatuzumab - a promising new immunotherapeutic agent. Expert Opin Investig Drugs 19(1):141-9, 2010. PMID: 19968579.
Rong-Hua T, Berkova Z, Wise J, Rezaeian AH, Daniluk U, David XA, Hawke H, Karp JE, Lin HK, Molldrem JJ, and Samaniego F. PMLRARα binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo. accepted, Blood.
Office: MDA FC 6.2030 (Unit 429)
Title: Associate Professor
M.D. - Harvard Medical School - 1983