Groundbreaking medical research offers Sanford Markowitz the best of two worlds. He thrives on solving tough scientific puzzles that come with medical research in a top-flight academic center. He also finds immense gratification that his work may someday help someone with serious illness such as colon cancer.
Profound dedication to colon cancer and oncology research has earned Markowitz a major Case Western Reserve University honor: 2015 Distinguished University Professor. He joined Donald L. Feke, vice provost for graduate education, and Ica Manas-Zloczower, engineering professor, in receiving Distinguished University Professor honors during fall convocation Wednesday, Aug. 26.
Markowitz serves as head of the Cancer Genetics Program of the Case Comprehensive Cancer Center and as principal investigator of the Case GI Cancers SPORE Center, an NCI-designated program of research excellence in gastrointestinal cancers. He also is an attending physician at the Seidman Cancer Center at University Hospitals Case Medical Center.
“My lab group and I are always looking for opportunities to do things that might directly help people with diseases,” he said. “When we do fundamental research, it is to understand better a problem posed to us by someone who is ill.”
Most notable have been Markowitz’s discoveries in colon cancer. The illness is of direct personal interest to him because his father was diagnosed with colon cancer when Markowitz served as an intern, which made the disease a natural focus for his research.
Markowitz discovered two key colon cancer tumor suppressor genes, TGF-beta RII and 15-PGDH. His work on TGF-beta RII explained why individuals with Lynch syndrome develop familial colon cancer—they are born with a molecular defect that leads to rapid inactivation of TGF-beta RII. His work on 15-PGDH led to the discovery of why aspirin prevents colon cancers in some individuals but not others. The effectiveness of aspirin chemoprevention depends on individuals having high colon expression of 15-PGDH.
This noteworthy 15-PGDH colon cancer research was done in collaboration with Harvard University. The collaboration was catalyzed by Markowitz and Harvard investigators working with former CBS Evening News anchor Katie Couric through the organization she co-founded, the Entertainment Industry Foundation’s National Colorectal Cancer Research Alliance.
“The work with Katie increased national awareness of the need for cancer screening, supported direct research in my lab, and fostered collaborations across the country between my lab and other leading colon cancer researchers,” Markowitz said. “These collaborations have allowed us to accomplish more together than what we could have on our own.”
Markowitz’s research further showed that 15-PGDH also functions as a key regulator of the ability of tissue stem cells to repair tissue injury and damage. With this discovery, Markowitz led a team that developed the first small molecule inhibitor of 15-PGDH. His findings showed that treating mice with this compound induced faster tissue repair and regeneration in multiple different organs. This included faster regeneration of normal bone marrow after a bone marrow transplant, faster regrowth of liver after liver surgery, and faster healing of ulcerative colitis. This compound is undergoing examination for development as a potential drug for human use.
Markowitz was a member of the team that sequenced the first complete human cancer genome (the colon cancer genome). He then co-led the team that discovered a different and unique set of genes responsible for colon cancers that develop in African-Americans compared to colon cancers of Caucasians. Lastly, Markowitz was one of the pioneers inventing testing for methylated-DNA in stools for early detection of colon cancer, an approach that is now FDA-approved. Markowitz and collaborators recently initiated human clinical trials of a similar test for early detection of esophageal cancers and pre-cancers.
Since 1987, Markowitz has served as lead or contributing author of 155 scientific papers in peer-reviewed medical journals and has secured 22 patents and licensed inventions.
Over the years, Markowitz has treasured his role as an educator, having mentored “extraordinary trainees” from many walks of clinical or medical research science.
“The people who work with you and who you train become a family in many ways,” Markowitz said. “I take tremendous pride and great pleasure in the successes that our lab’s alumni have accomplished in their own right.”
He also praised the scientists in his lab who have taken ideas and turned them into experiments with real-life results and the contributions of collaborators from other science disciplines at the university. Markowitz particularly credits the support of Stanton L. Gerson, MD, director of the Case Comprehensive Cancer Center, and past cancer center directors James K.V. Willson, MD, and Nathan A. Berger, MD, plus ongoing scientific collaborations with Gerson, Joseph Willis MD, Amitabh Chak MD, and Kishore Guda DVM, PhD. Finally, he thanked Case Western Reserve and University Hospitals for affording tremendous intellectual freedom.
“I am at a wonderful institution with terrific colleagues,” Markowitz said. “No one has ever closed the door on me when I asked for help with a project we are working on.”