September 2024

UROLOGY

SARKI A. ABDULKADIR, MD, PHD: ADVANCING BASIC SCIENCE RESEARCH FROM BENCH TO BEDSIDE

Sarki A. Abdulkadir, MD, PhD, is the John T. Grayhack Professor of Urological Research, vice chair for Research at Northwestern Medicine. In addition to a variety of other roles, he serves as co-director of Cancer Global Health and associate director for diversity, equity and inclusion at Robert H. Lurie Comprehensive Cancer Center at Northwestern Medicine.

Having authored more than 65 peer-reviewed publications, Dr. Abdulkadir is also currently the principal investigator on three NIH grants; two R01 awards and a P50 award. The latter is part of the Specialized Program of Research Excellence (SPORE) in prostate cancer at Lurie Cancer Center, where he is associate director for Translational Research. This SPORE is one of only seven such grants in the country.  
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Dr. Abdulkadir is member of the American Society for Clinical Investigation and serves on the editorial board of the Journal of Clinical Investigation. He won the 2020 Tripartite Legacy Faculty Prize in Translational Science and Education at Northwestern University Feinberg School of Medicine; the award recognized his excellence in research that emphasizes translational approaches, teaching and mentoring, and leadership. According to the most recent NIH data compiled by Blue Ridge Institute for Medical Research, Dr. Abdulkadir is the highest-funded urologic principal investigator in the United States.
Dr. Abdulkadir’s research focuses on understanding the molecular mechanisms that drive prostate cancer initiation, progression and recurrence. He has a strong interest in genomics and gene regulation; oncogenic kinases as molecular therapeutic targets; as well as the use of in vivo lineage tracing to define the fates of specific cell populations in tumorigenesis.
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His work has shed light on the cellular origins of prostate cancer, cancer gene cooperation in tumorigenesis and the development of novel therapeutic agents currently in preclinical and clinical development. 

Breakthrough Discoveries in the Abdulkadir Lab

The Sarki Abdulkadir Lab at Northwestern Medicine, run by Dr. Abdulkadir, is dedicated to understanding the molecular mechanisms of prostate cancer and developing targeted therapies. Making landmark discoveries, Dr. Abdulkadir and his team have identified genetic mutations that help jumpstart prostate cancer growth. These findings have led to the design of small molecules to block cancer-causing proteins such as MYC. Because MYC proteins play a role in 70% of all human cancers, they have been an attractive target for cancer therapy. Yet several structural aspects of going after the protein, including potential harm to healthy tissues, have deemed it “undruggable” — until recently thanks to innovative genetic modeling studies.

In animal models, the team has made significant headway in identifying a series of MYC inhibitors that offer favorable pharmacokinetic profiles to help silence MYC expression and remodel the tumor-immune microenvironment. Currently, the team is developing several novel MYC inhibitor compounds.

Additionally, the Abdulkadir Lab has identified a gene — PRRX2 — that appears to be involved in the development of resistance to a commonly used prostate cancer treatment: androgen receptor pathway inhibitors (ARPIs). Many metastatic prostate cancers eventually become resistant to standard therapy and become AR-negative. Patients with upregulated PRRX2 tend to have worse survival compared to other patients, especially those who are AR-negative. While much is still unknown about this gene and its connection to androgen insensitivity, it offers potential to mitigate these pathways by inhibiting them downstream. This research offers hope in finding solutions for the growing numbers of patients that fail therapy because they become AR-negative.
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Learn more about the Sarki Abdulkadir Lab at Northwestern Medicine.

Recent High-Impact Research From Dr. Abdulkadir

Genes May Predict Treatment Resistance in Prostate Cancer​
​Increased expression of specific genes in patients with prostate cancer may predict if the cancer will respond well to hormone therapy, according to a new study published in Nature Communications. Dr. Abdulkadir was a co-author of the study.

Genome-Wide Intricacies of Cancer Inhibitor Untangled
A newly discovered inhibitor of a common cancer-causing protein operates selectively, reducing expression of genes that fuel rampant cell proliferation and alter the epigenome, according to a Northwestern Medicine study published in Science Advances. Dr. Abdulkadir was the co-senior author of the study.

New Regulator of Therapy Resistance in Prostate Cancer​
Northwestern Medicine investigators have identified a gene that confers resistance to a common prostate cancer treatment, according to a study published in Cancer Research. According to Dr. Abdulkadir, targeting the pathway downstream from this gene could reverse therapeutic resistance and improve outcomes for patients with prostate cancer.

New Drug Target for Treatment-Resistant Prostate Cancer
​Northwestern Medicine scientists have discovered a new target for slowing treatment-resistant prostate cancer, according to a recent study published in Nature Communications. Inhibiting an epigenetic regulator called DOT1L reduced growth of human prostate tumor cells while sparing healthy cells, says Dr. Abdulkadir.

​Overcoming Hormone Therapy Resistance in Prostate Cancer with Sarki Abdulkadir, MD, PhD
Dr. Abdulkadir details how his research, recently published in Nature Communications, is a significant step toward understanding and treating treatment-resistant prostate cancer. 
Sarki Abdulkadir, MD, PhD, the John T. Grayhack, MD, Professor of Urological Research and Vice Chair for Research in the Department of Urology

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