Asfar S. Azmi, PhD
Karmanos Cancer Institute
4100 John R, HWCRC 740.1
Detroit MI 48201
Mentoring: Gabriel Mpilla ( Year 2 )
- Nuclear protein transport biology in cancer development, progression and drug resistance
- Rho GTPases in cancer drug resistance
- Novel therapeutic avenues in mutant Kras pathway
- Animal models in translational drug discovery
Dr. Azmi's lab has a long standing interest in understanding the role of aberrant nuclear protein transport in cancer development, progression and drug resistance. Exportin 1 (XPO1) also known as chromosome maintenance region 1 (CRM1) is the major exporter of majority of tumor suppressor and genome surveillance proteins. Dr. Azmi's team has defined the role of disturbed XPO1 activity in pancreatic cancer and non-Hodgkin's lymphoma and demonstrated it to be a therapeutic target for these difficult to treat malignancies. His lab was instrumental in translating the nuclear export inhibitor Selinexor into the clinic for several solid tumors and hematological malignancies. The drug Selinexor was tested in pre-clinical models of pancreatic cancer in his lab and led to a Phase Ib/II clinical study at Karmanos Cancer Institute. Other Phase II trials in hematological malignancies are also ongoing. Using high throughput methodologies, his lab is defining the epigenetic and regulatory mechanisms of XPO1 and identifying novel drug combinations that could enhance the anti-cancer activity of nuclear export inhibitors. Dr. Azmi's group is also developing novel drugs against mutant KRas pathway proteins. His team has discovered the role of Rho GTPase effector protein p21-activated kinase 4 (PAK4) in promoting pancreatic cancer "stem-ness", desmoplasia and drug resistance in cellular and animal models. His ongoing projects are especially focused on developing ways to favorably alter the pancreatic tumor microenvironment, making them more accessible to chemotherapeutic drugs. His lab is also exploring how targeting PAK4 and other KRas pathway proteins can enhance immunotherapy strategies in therapy resistant cancers.
Azmi AS, Li Y, Muqbil I, Aboukameel A, Senapedis W, Baloglu E, Landesman Y, Shacham S, Kauffman MG, Philip PA, 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 Jul 17. [Epub ahead of print]
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.
Ning C, Liang M, Liu S, Wang G, Edwards H, Xia Y, Polin L, Dyson G, Taub JW, Mohammad RM, Azmi AS, Zhao L, Ge Y. Targeting ERK enhances the cytotoxic effect of the novel PI3K and mTOR dual inhibitor VS-5584 in preclinical models of pancreatic cancer. Oncotarget. 2017;8:44295-311.
Aboukameel A, Muqbil I, Senapedis W, Baloglu E, Landesman Y, Shacham S, Kauffman M, Philip PA, Mohammad RM, Azmi AS. Novel p21-Activated Kinase 4 (PAK4) Allosteric Modulators Overcome Drug Resistance and Stemness in Pancreatic Ductal Adenocarcinoma. Mol Cancer Ther. 2017;16:76-87.
Azmi AS, Mohammad RM. Targeting Cancer at the Nuclear Pore. J Clin Oncol. 2016;34:4180-82.
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;383:309-317.
Kashyap T, Argueta C, Aboukameel A, Unger TJ, Klebanov B, Mohammad RM, Muqbil I, Azmi AS, Drolen C, Senapedis W, Lee M, Kauffman M, Shacham S, Landesman Y. Selinexor, a Selective Inhibitor of Nuclear Export (SINE) compound, acts through NF-κB deactivation and combines with proteasome inhibitors to synergistically induce tumor cell death. Oncotarget. 2016;7:78883-95.
Diab M, Muqbil I, Mohammad RM, Azmi AS, Philip PA. The Role of microRNAs in the Diagnosis and Treatment of Pancreatic Adenocarcinoma. J Clin Med. 2016;5(6).
Sukari A, Muqbil I, Mohammad RM, Philip PA, Azmi AS. F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities. Semin Cancer Biol. 2016;36:95-104.
Azmi AS. Opening a Pandora's (F)-box in cancer. Semin Cancer Biol. 2016;36:1-2.
Education and Training:
PhD. (2006) AMU, India
Cancer Biology Courses Taught:
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling
CB7700 Recent Developments in Cancer Biology