Ramzi Mohammad
Office Address
Karmanos Cancer Institute
732 HWCRC
4100 John R.
Detroit, MI 48201
Department
Oncology
Research Interests
• GI-cancers including pancreatic cancer
• Translational research
• Animal models
• Cancer drug discovery
Research Description
Dr. Mohammad has more than 30 years of cancer research experience, including experience in molecular biology, animal models and tissue culture. His lab has established a number of pancreatic cancer and other hematological malignancies cell lines, in which he has years of experience in studying the effects of new anticancer agents, marine products, small molecule inhibitors as well as new natural products. Dr. Mohammad's research is translational in nature through his close work with clinicians.
His lab has introduced several anticancer drugs to the clinic. Among them are 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. Currently, our 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 lab has a long-standing interest in understanding the role of active ingredients in natural products such as Thymoquinone from Black seeds (Nigella sativa) and others. Dr. Mohammad’s lab has demonstrated the synergistic effect of Thymoquinone when combined with several anticancer agents against pancreatic cancer, colon cancer and lymphoma.
The abnormal upregulation or downregulation of specific miRNAs in cancer cells could be due to the hypomethylation or hypermethylation of specific miRNA gene DNAs. Therefore, it is important to reveal the regulatory mechanism(s) in the DNA methylation/miRNA/mRNA/protein axis for a specific miRNA regulation loop in order to design the novel therapeutic strategy for the treatment of pancreatic cancer. Recently Dr. Mohammad’s lab is involved in epigenetic research and has published on the role of DNA-Methylation-caused downregulation of miR-30 and the aggressive growth of pancreatic cancer.
Selected publications
Khan HY, Nagasaka M, Li Y, Aboukameel A, Uddin MH, Sexton R, Bannoura S, Mzannar Y, Al-Hallak MN, Kim S, Beydoun R, Landesman Y, Mamdani H, Uprety D, Philip PA, Mohammad RM, Shields AF, Azmi AS. Inhibitor of the Nuclear Transport Protein XPO1 Enhances the Anticancer Efficacy of KRAS G12C Inhibitors in Preclinical Models of KRAS G12C-Mutant Cancers. Cancer Res Commun. 2022;2:342-52
Li Y, Azmi AS, Mohammad RM. Deregulated transcription factors and poor clinical outcomes in cancer patients. Semin Cancer Biol. 2022:S1044-579X00181-X.
Azmi AS, Uddin MH, Mohammad RMThe nuclear export protein XPO1 - from biology to targeted therapy. Nat Rev Clin Oncol. 2021;18:190.
Al-Share B, Alloghbi A, Al Hallak MN, Uddin H, Azmi A, Mohammad RM, Kim SH, Shields AF, Philip PA. Gastrointestinal stromal tumor: a review of current and emerging therapies. Cancer Metastasis Rev. 2021;40:625-41.
Mpilla GB, Uddin MH, Al-Hallak MN, Aboukameel A, Li Y, Kim SH, Beydoun R, Dyson G, Baloglu E, Senapedis WT, Landesman Y, Wagner KU, Viola NT, El-Rayes BF, Philip PA, Mohammad RM, Azmi ASPAK4-NAMPT Dual Inhibition Sensitizes Pancreatic Neuroendocrine Tumors to Everolimus. Mol Cancer Ther. 2021;20:1836-45.
Uddin MH, Al-Hallak MN, Philip PA, Mohammad RM, Viola N, Wagner KU, Azmi AS. Exosomal microRNA in Pancreatic Cancer Diagnosis, Prognosis, and Treatment: From Bench to Bedside. Cancers (Basel). 2021;13:2777.
Li Y, Al Hallak MN, Philip PA, Azmi AS, Mohammad RM. Non-Coding RNAs in Pancreatic Cancer Diagnostics and Therapy: Focus on lncRNAs, circRNAs, and piRNAs. Cancers (Basel). 2021;13:4161.
Seymour EK, Khan HY, Li Y, Chaker M, Muqbil I, Aboukameel A, Ramchandren R, Houde C, Sterbis G, Yang J, Bhutani D, Pregja S, Reichel K, Huddlestun A, Neveux C, Corona K, Landesman Y, Shah J, Kauffman M, Shacham S, Mohammad RM, Azmi AS, Zonder JA.Selinexor in Combination with R-CHOP for Frontline Treatment of Non-Hodgkin Lymphoma: Results of a Phase I Study. Clin Cancer Res. 2021;27:3307-16.
Khan HY, Uddin MH, Balasubramanian SK, Sulaiman N, Iqbal M, Chaker M, Aboukameel A, Li Y, Senapedis W, Baloglu E, Mohammad RM, Zonder J, Azmi AS.PAK4 and NAMPT as Novel Therapeutic Targets in Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell Lymphoma. Cancers (Basel). 2021;14:160
Khan HY, Mpilla GB, Sexton R, Viswanadha S, Penmetsa KV, Aboukameel A, Diab M, Kamgar M, Al-Hallak MN, Szlaczky M, Tesfaye A, Kim S, Philip PA, Mohammad RM, Azmi AS.Calcium Release-Activated Calcium (CRAC) Channel Inhibition Suppresses Pancreatic Ductal Adenocarcinoma Cell Proliferation and Patient-Derived Tumor Growth. Cancers (Basel). 2020;12:750
Teslow EA, Mitrea C, Bao B, Mohammad RM, Polin LA, Dyson G, Purrington KS, Bollig-Fischer A.Obesity-induced MBD2_v2 expression promotes tumor-initiating triple-negative breast cancer stem cells. Mol Oncol. 2019;13:894-908.
Mpilla G, Aboukameel A, Muqbil I, Kim S, Beydoun R, Philip PA, Mohammad RM, Kamgar M, Shidham V, Senapedis W, Baloglu E, Li J, Dyson G, Xue Y, El-Rayes B, Azmi AS.PAK4-NAMPT Dual Inhibition as a Novel Strategy for Therapy Resistant Pancreatic Neuroendocrine Tumors. Cancers (Basel). 2019;11:1902
Muqbil I, Chaker M, Aboukameel A, Mohammad RM, Azmi AS, Ramchandren. Pre-clinical anti-tumor activity of Bruton's Tyrosine Kinase inhibitor in Hodgkin's Lymphoma cellular and subcutaneous tumor model. Heliyon. 2019;5:e02290.
Khan HY, Ge J, Nagasaka M, Aboukameel A, Mpilla G, Muqbil I, Szlaczky M, Chaker M, Baloglu E, Landesman Y, Mohammad RM, Azmi AS, Sukari A.Targeting XPO1 and PAK4 in 8505C Anaplastic Thyroid Cancer Cells: Putative Implications for Overcoming Lenvatinib Therapy Resistance. Int J Mol Sci. 2019;21:237
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. 2019;10:367-77
Azmi AS, Li Y, Aboukameel A, Muqbil I, Philip PA, Mohammad RM.DNA-Methylation-Caused Downregulation of miR-30 Contributes to the High Expression of XPO1 and the Aggressive Growth of Tumors in Pancreatic Ductal Adenocarcinoma. Cancers (Basel). 2019;11:1101.
Education/Training
PhD in Stress Physiology (1987): Utah State University, Logan, Utah
Post-Doc in Cancer Biology (1991): Wayne State University, Detroit, Michigan
Courses Taught
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling