Asfar S. Azmi, PhD
Karmanos Cancer Institute
4100 John R, HWCRC 740.1,
Detroit MI 48201
- 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.
Aboukameel A, Muqbil I, Wu J, Senapedis W, Baloglu E, Bollig-Fischer A, Dyson G, Kauffman M, Landesman Y, Shacham S, Philip PA, Mohammad RM and Azmi AS. Novel p21-activated kinase 4 (PAK4) allosteric modulators overcome drug resistance and stemness in pancreatic ductal adenocarcinoma. Molecular Cancer Therapeutics. Mol Cancer Ther. 2017;16:76-87.
Azmi AS, Mohammad RM, P21 activated kinase 4 (PAK4): a therapeutic target in the elusive Kras pathway. Future Medicinal Chemistry. 2015;5-7.
Azmi AS, Mohammad RM. Targeting cancer at the nuclear pore. Journal of Clinical Oncology. 2015.65.3949.
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.
Azmi AS. The evolving role of nuclear transporters in cancer. Semin Cancer Biol. 2014;27:1-2.
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.
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.
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.
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