School of Medicine

Wayne State University School of Medicine

Ramzi Mohammad

 

 

 

 

 

 

Ramzi M. Mohammad, Ph.D.
Professor - Department of Oncology
Director GI Research
Wayne State University
Karmanos Cancer Institute
732 HWCRC
4100 John R.
Detroit, MI 48201
313-576-8329
mohammar@karmanos.org

Research Interests:

  • 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.

Research Description:
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.

Selected Publications:

Muqbil I, Wu J, Aboukameel A, Mohammad RM, Azmi AS. Snail nuclear transport: the gateways regulating epithelial-to-mesenchymal transition? Semin Cancer Biol. 2014;27:39-45.

Gao J, Azmi AS, Aboukameel A, Kauffman M, Shacham S, Abou-Samra AB, Mohammad RM. Nuclear retention of Fbw7 by specific inhibitors of nuclear export leads to Notch1 degradation in pancreatic cancer. Oncotarget. 2014;5:3444-54.

Rodrigueza WV, Woolliscroft MJ, Ebrahim AS, Forgey R, McGovren PJ, Endert G, Wagner A, Holewa D, Aboukameel A, Gill RD, Bisgaier CL, Messmann RA, Whitehead CE, Izbicka E, Streeper R, Wick MC, Stiegler G, Stein CA, Monsma D, Webb C, Sooch MP, Panzner S, Mohammad R, Goodwin NC, Al-Katib A. Development and antitumor activity of a BCL-2 targeted single-stranded DNA oligonucleotide. Cancer Chemother Pharmacol. 2014;74:151-66.

Bao B, Ali S, Ahmad A, Li Y, Banerjee S, Kong D, Aboukameel A, Mohammad R, Van Buren E, Azmi AS, Sarkar FH. Differentially expressed miRNAs in cancer-stem-like cells: markers for tumor cell aggressiveness of pancreatic cancer. Stem Cells Dev. 2014;23:1947-58.

Azmi AS, Mohammad RM. Rectifying cancer drug discovery through network pharmacology. Future Med Chem. 2014;6:529-39.

Choudhry ZS, Tripathi V, Sutton M, Bao B, Mohammad RM, Azmi AS. Regulation of KRAS-PAK4 Axis by MicroRNAs in Cancer. Curr Pharm Des. 2014;20:5275-8.

Sahin K, Orhan C, Tuzcu M, Muqbil I, Sahin N, Gencoglu H, Guler O, Padhye SB, Sarkar FH, Mohammad RM. Comparative in vivo evaluations of curcumin and its analog difluorinated curcumin against cisplatin-induced nephrotoxicity. Biol Trace Elem Res. 2014;157:156-63.

Abulwerdi F, Liao C, Liu M, Azmi AS, Aboukameel A, Mady AS, Gulappa T, Cierpicki T, Owens S, Zhang T, Sun D, Stuckey JA, Mohammad RM, Nikolovska-Coleska Z. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2014;13:565-75.

Muqbil I, Kauffman M, Shacham S, Mohammad RM, Azmi AS. Understanding XPO1 target networks sing systems biology and mathematical modeling. Curr Pharm Des. 2014;20:56-65.

Bener A, Darwish S, Al-Hamaq AO, Mohammad RM, Yousafzai MT. Association of PPARγ2 gene variant Pro12Ala polymorphism with hypertension and obesity in the aboriginal Qatari population known for being consanguineous. Appl Clin Genet. 2013;6:103-11.

Azmi AS, Mohammad RM. Providing activation-induced cytidine deaminase (AID) to nuclear export inhibitors. Response to: "Complex downstream effects of nuclear export inhibition in B-cell lymphomas: a possible role for activation-induced cytidine deaminase". Haematologica. 2013;98:e123.

Azmi AS, Bollig-Fischer A, Bao B, Park BJ, Lee SH, Yong-Song G, Dyson G, Reddy CK, Sarkar FH, Mohammad RM. Systems analysis reveals a transcriptional reversal of the mesenchymal phenotype induced by SNAIL-inhibitor GN-25. BMC Syst Biol. 2013;7:85.

Muqbil I, Bao B, Abou-Samra AB, Mohammad RM, Azmi AS. Nuclear export mediated regulation of microRNAs: potential target for drug intervention. Curr Drug Targets. 2013;14:1094-100.

Azmi AS, Al-Katib A, Aboukameel A, McCauley D, Kauffman M, Shacham S, Mohammad RM. Selective inhibitors of nuclear export for the treatment of non-Hodgkin's lymphomas. Haematologica. 2013;98:1098-106.

Muqbil I, Bao B, Abou-Samra AB, Mohammad RM, Azmi AS. Nuclear export mediated regulation of microRNAs: potential target for drug intervention. Curr Drug Targets. 2013;14:1094-100.

Muqbil I, Kauffman M, Shacham S, Mohammad RM, Azmi AS. Understanding XPO1 Target Networks Using Systems Biology and Mathematical Modeling. Curr Pharm Des. 2013 Mar 19.

Alian OM, Shah M, Mohammad M, Mohammad RM. Network pharmacology: reigning in drug attrition? Curr Drug Discov Technol. 2013;10:155-9.

Azmi AS, Bao GW, Gao J, Mohammad RM, Sarkar FH. Network insights into the genes regulated by hepatocyte nuclear factor 4 in response to drug induced perturbations: a review. Curr Drug Discov Technol. 2013;10:147-54.

Azmi AS, Aboukameel A, Bao B, Sarkar FH, Philip PA, Kauffman M, Shacham S, Mohammad RM. Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice.
Gastroenterology. 2013;144:447-56.

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