Ramzi M. Mohammad, Ph.D.
Professor - Department of Oncology
Director GI Research
Wayne State University
Karmanos Cancer Institute
4100 John R.
Detroit, MI 48201
- Dr. Mohammad's research is translational in nature and through his close work with clinicians he was able to introduce several experimental drugs into the clinic among which include Bryostatin-1, Aurastatin-PE, Dolastatin-10 and CA-4 (cambertastatin-4) and other small molecule inhibitors of Bcl-2 such as AT-101 (gossypol) and HMD2.
- Dr. Mohammad is currently involved in GI-cancer research and works in close association with GI physicians at KCI.
Death (apoptosis) is a distinct cellular process and promising a new avenue for targeted cancer chemotherapy. Cells have anti-apoptotic proteins which, function by neutralizing pro-apoptotic proteins. The balance between anti- and pro-apoptotic processes decides life or death for the cell. We have new BH3-mimetic small molecule inhibitors (SMIs) that disarm anti-apoptotic Bcl2-family proteins, by displacing natural pro-apoptotic proteins which use their BH3 domain to bind to Bcl-2. We have established mouse xenograft models from pancreatic cancer, colon cancer and lymphoma and leukemia, facilitating studies of drug efficacy and mechanism of action in vivo. Our SMIs disarm a broader spectrum of anti-apoptotic proteins, including Mcl-1. In my laboratory, we study efficacy and mechanism of action of these novel BH3-mimetic SMIs in cultured cells and animal models. The second program involves inhibition of HDM2 (Human double Minute 2), a protein that regulates the activity of another important component of the apoptotic pathway, the p53 tumor suppressor protein. In cells with wild-type p53, the HDM2 protein binds to p53 in cancer cells and inhibits its activity. Inhibition of the interaction between HDM2 and p53 stimulates p53 activity and subsequently apoptosis. A new and promising approach for the development of anticancer agents is the inhibition of the HDM2-p53 interaction using non-peptide small-molecule inhibitors. Currently, my lab is investigating several SMIs including novel HDM2 inhibitors and Mcl-1 inhibitors. Since these SMIs induce apoptosis, they synergize with traditional cytotoxic drugs commonly used in the clinic, hence increasing the cure rate in some pancreatic and colon cancers.
Dr. Mohammad has more than 25 years of cancer research experience, including extensive experience in molecular biology, animal models and tissue culture. He has established a number of pancreatic cancer and other hematological malignancies cell lines and was among the first to establish pancreatic orthotopic models, in which he has years of experience in studying the effects of new anticancer agents, marine products as well as standard chemotherapeutic drugs. Dr. Mohammad's research is translational in nature and through his close work with clinicians.
Mohammad RM, Li Y, Muqbil I, Aboukameel A, Senapedis W, Baloglu E, Landesman Y, Philip PA, Azmi AS. Targeting Rho GTPase effector p21 activated kinase 4 (PAK4) suppresses p-Bad-microRNA drug resistance axis leading to inhibition of pancreatic ductal adenocarcinoma proliferation. Small GTPases. 2017 Jun 22:0. [Epub ahead of print].
Azmi AS, Li Y, Muqbil I, Aboukameel A, Senapedis W, Baloglu E, Landesman Y, Shacham S, Kauffman MG, Philip PA and Mohammad RM. Exportin 1 (XPO1) inhibition leads to restoration of tumor suppressor miR-145 and consequent suppression of pancreatic cancer cell proliferation and migration. Oncotarget 2017;8:82144-55. (Data analysis, writing manuscript).
Bao B, Mitrea C, Wijesinghe P, Marchetti L, Girsch E, Farr RL, Boerner JL, Mohammad R, Dyson G, Terlecky SR, Bollig-Fischer A. Treating triple negative breast cancer cells with erlotinib plus a select antioxidant overcomes drug resistance by targeting cancer cell heterogeneity. Sci Rep. 2017;7:44125. Ramzi M. Mohammad, Ph.D. Page 30.
Siveen KS, Uddin S, Mohammad RM. Targeting acute myeloid leukemia stem cell signaling by natural products. Mol Cancer. 2017;16:13. Review.
Khan MA, Khan S, Windpassinger C, Badar M, Nawaz Z, Mohammad RM. The Molecular Genetics of Autosomal Recessive Nonsyndromic Intellectual Disability: a Mutational Continuum and Future Recommendations. Ann Hum Genet. 2016 Nov;80(6):342-368.
Azmi AS, Mohammad RM. Targeting Cancer at the Nuclear Pore. J Clin Oncol. 2016;34:4180-82.
Halama A, Kulinski M, Kader SA, Satheesh NJ, Abou-Samra AB, Suhre K,Mohammad RM. Measurement of 1,5-anhydroglucitol in blood and saliva: from non-targeted metabolomics to biochemical assay. J Transl Med. 2016;14:140.
Muqbil I, Aboukameel A, Elloul S, Carlson R, Senapedis W, Baloglu E, Kauffman M, Shacham S, Bhutani D, Zonder J, Azmi AS, Mohammad RM. Anti-tumor activity of selective inhibitor of nuclear export (SINE) compounds, is enhanced in non-Hodgkin lymphoma through combination with mTOR inhibitor and dexamethasone. Cancer Lett. 2016;383:309-17.
Mohammad RM, Muqbil I, Lowe L, et al. Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol. 2015;35 Suppl:S78-S103.
Muqbil I, Mohammad RM. Selecting efficacious Bcl-2 family inhibitors for optimal clinical outcome. Ann Transl Med. 2015;3:312.
Azmi AS, Muqbil I, Wu J, Aboukameel A, Senapedis W, Baloglu E, Bollig-Fischer A, Dyson G, Kauffman M, Landesman Y, Shacham S, Philip PA, Mohammad RM. Targeting the Nuclear Export Protein XPO1/CRM1 Reverses Epithelial to Mesenchymal Transition. Sci Rep. 2015;5:16077.
Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin AR, Amin A, Aquilano K, Arbiser J, Arreola A, Arzumanyan A, Mohammad RM, et al. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin Cancer Biol. 2015;35 Suppl:S276-304.
Azmi AS, Mohammad RM, P21 activated kinase 4 (PAK4): a therapeutic target in the elusive Kras pathway. Future Medicinal Chemistry. 2015;7:5-7.
Education and Training:
PhD in Stress Physiology (1987): Utah State University, Logan, Utah
Post-Doc in Cancer Biology (1991): Wayne State University, Detroit, Michigan
Cancer Biology Courses Taught:
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling