Office Address

Karmanos Cancer Institute
4100 John R, HWCRC 740.1
Detroit MI 48201

Mentoring

Gabriel Mpilla and Rachel Sexton

Research Interests

• Pancreatic Cancer
• Nuclear protein transport biology in cancer
• Novel therapeutic avenues in mutant KRAS pathway
• NAD Signaling
• Animal models in translational drug discovery
 

Research Description

Dr. Asfar Azmi is the co-leader of the tumor biology and microenvironment research program and the director of the pancreatic cancer research initiative at Karmanos Cancer Institute, Wayne State University School of Medicine. His lab has a long-standing interest in understanding the role of aberrant nuclear protein transport in cancer development and drug resistance. Exportin 1 (XPO1) also known as chromosome maintenance region 1 (CRM1) is the major nuclear 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. His groups established the efficacy of nuclear transport targeted drugs in pre-clinical models and this work led to several Phase Ib/II clinical studies at Karmanos Cancer Institute. Work done by his team was instrumental in the FDA approval of selinexor for refractory multiple myeloma. 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) and nicotinamide adenine dinucleotide (NAD) biosynthesis pathway rate limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT) in promoting tumor growth, desmoplasia and drug resistance in cellular and patient derived tumor models. His ongoing projects are 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 KRAS pathway proteins and NAD signaling can enhance immunotherapy strategies in therapy resistant cancers.

Recent Publications

Nagasaka M, Li Y, Sukari A, Ou SI, Al-Hallak MN, Azmi AS. KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne? Cancer Treat Rev. 2020;84:101974.

Nagasaka M, Sexton R, Alhasan R, Rahman S, Azmi AS, Sukari A. Gut microbiome and response to checkpoint inhibitors in non-small cell lung cancer-A review. Crit Rev Oncol Hematol. 2020 Jan;145:102841.

Azmi AS, Khan HY, Muqbil I, Aboukameel A, Neggers JE, Daelemans D, Mahipal A, Dyson G, Kamgar M, Al-Hallak MN, Tesfaye A, Kim S, Shidham V, M Mohammad R, Philip PA. Preclinical Assessment with Clinical Validation of Selinexor with Gemcitabine and Nab-Paclitaxel for the Treatment of Pancreatic Ductal Adenocarcinoma.Clin Cancer Res. 2020;26:1338-48.

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;pii: E237.

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:pii: E1902.

Sexton R, Mahdi Z, Chaudhury R, Beydoun R, Aboukameel A, Khan HY, Baloglu E, Senapedis W, Landesman Y, Tesfaye A, Kim S, Philip PA, Azmi AS. Targeting Nuclear Exporter Protein XPO1/CRM1 in Gastric Cancer. Int J Mol Sci. 2019;20:E4826.

Muqbil I, Chaker M, Aboukameel A, Mohammad RM, Azmi AS, Ramchandren R. Pre-clinical anti-tumor activity of Bruton's Tyrosine Kinase inhibitor in Hodgkin's Lymphoma cellular and subcutaneous tumor model. Heliyon. 2019;5:e02290.

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:pii: E1101.

Sexton RE, Mpilla G, Kim S, Philip PA, Azmi AS. Ras and exosome signaling. Semin Cancer Biol. 2019;54:131-7.

Diab M, Azmi A, Mohammad R, Philip PA. Pharmacotherapeutic strategies for treating pancreatic cancer: advances and challenges. Expert Opin Pharmacother. 2019;20:535-46.

Tesfaye AA, Azmi AS, Philip PA. miRNA and Gene Expression in Pancreatic Ductal Adenocarcinoma. Am J Pathol. 2019;189:58-70.

Aboukameel A, Muqbil I, Baloglu E, Senapedis W, Landesman Y, Argueta C, Kauffman M, Chang H, Kashyap T, Shacham S, Neggers JE, Daelemans D, Heath EI, Azmi AS. Down-regulation of AR splice variants through XPO1 suppression contributes to the inhibition of prostate cancer progression. Oncotarget. 2018;9:35327-42.

Azmi AS. Nuclear export mechanisms of circular RNAs: size does matter. Noncoding RNA Investig. 2018;2:pii: 52.

Azmi AS. Some chinks in RAS armor. Semin Cancer Biol. 2019;54:iii-iv.

Muqbil I, Azmi AS, Mohammad RM. Nuclear Export Inhibition for Pancreatic Cancer Therapy. Cancers (Basel). 2018;10:pii: E138.

Gawde KA, Sau S, Tatiparti K, Kashaw SK, Mehrmohammadi M, Azmi AS, Iyer AK. Paclitaxel and di-fluorinated curcumin loaded in albumin nanoparticles for targeted synergistic combination therapy of ovarian and cervical cancers. Colloids Surf B Biointerfaces. 2018;167:8-19.

Tesfaye AA, Kamgar M, Azmi A, Philip PA. The evolution into personalized therapies in pancreatic ductal adenocarcinoma: challenges and opportunities. Expert Rev Anticancer Ther. 2018;18:131-48

Education/Training

PhD. (2006) AMU, India

Courses Taught

CB7300 Special Topics - Fundamentals of Cancer Drug Discovery
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling
CB7700 Recent Developments in Cancer Biology
CB7300 Special Topics-Cancer Biomarkers
 

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