January 2015 Newsletter

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Department of Medicine eNewsletter
January 2015
:: Interview
:: Department News
:: Department Events
:: Leadership Council Minutes
Leadership Council
January 2015

Richard Walsh

B. Arafah

K. Armitage

A. Askari

R. Bonomo

R. Chandra

F. Cominelli

F. Creighton

S. Gravenstein

T. Hostetter

D. Hricik

N. Meropol

R. Salata

R. Schilz

D. Simon

R. Walsh

J. Wright


Recorded by:
A. Staruch
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department interview
Sanford Markowitz, MD, PhD, head of the Cancer Genetics Program at the Case Comprehensive Cancer Center and Principal Investigator of the Case GI Cancers SPORE center, analyzes his latest findings in colon cancer research and their implications, shares how the Harrington Discovery Institute at University Hospitals - part of the Harrington Project for Discovery & Development - revolutionized his work and discusses ways patients and their families are moving cancer research forward.

You have built an extensive portfolio of revolutionary research projects over the years. What are you currently working on?


A lot of our research is centered around the Gastrointestinal Cancers SPORE program, one of five national cancer research centers sponsored by National Institutes of Health (NIH) that includes our center along with Harvard, Hopkins, Michigan and Vanderbilt. Over the past six to 12 months, we have been focusing on identifying the factors that differentiate colon cancer in African-Americans from those in Caucasians. We know that colon cancers are more fatal when they occur in African-American population and we have just finished our first study examining gene mutation in the two populations. We have found that when colon cancer arises in African-Americans, it often has gene mutations we do not encounter among Caucasians, we suspect it is part of the reason why these tumors behave differently and we are working on developing new ways to detect and treat them effectively.


Another area we have been looking into is cancer of the esophagus. Esophagus cancer has significantly increased over the past 30 years and it is actually the fastest-growing cause of cancer death from solid tumors. It is quite striking because the mortality rate of so many other cancers has been diminishing during this time. We are trying to develop a way to detect esophagus cancer early on before it becomes lethal. Currently, most patients are not diagnosed with esophagus cancer until they develop symptoms and are examined by endoscopy. The problem with this approach is a lot of patients develop incurable cancers before symptoms bring them to the hospital. Our lab team, that includes Amitabh Chak, MD, and Joseph Willis, MD, is concentrating on identifying molecular changes that can be detected in esophagus cancer early on through DNA testing. In our work, we show that if you just put a brush in the esophagus and pull it back, you can test the DNA on the brush to detect the changes that identify the presence of precancers and cancers. We are currently trying to find a practical way to apply our findings to offer screening to people at low cost. Our team has also been developing a balloon-based device that a patient can comfortably swallow to perform an esophagus brushing without using an endoscope. In addition, we have been working on identifying new genetic changes that can differentiate between Barrett's esophagus, an early change, and actual esophagus cancers, and that could be used to catch early disease progression toward cancer in individuals with Barrett's.


Finally, our work has been moved into drug development. We have come across an important pathway that normally acts to stop cell division. Turning on this genetic switch should prevent cancers from growing. But turning it off should help tissues grow, and there are times in medicine when we do want to promote tissue growth, such as following an organ transplant. We took this idea to the Harrington Discovery Institute and developed what we think is a compound that could be used as a drug to help regrow tissues, particularly in a transplant setting. It's a whole new adventure for us as we have never done drug development before and are excited to do so with the help of the Harrington Discovery Institute.


The Harrington Discovery Institute is the nonprofit arm of the Harrington Project for Discovery & Development - centered at University Hospitals in Cleveland, Ohio. The Harrington Project is a national initiative supporting research by physician-scientists. You were selected to be part of the first class of Harrington Scholar-Innovator grant recipients in 2013. How did this opportunity influence your working environment? How has your research changed as a result of Harrington Discovery Institute support?


Support from the Harrington Discovery Institute has really been revolutionary in terms of its effect on our research. We were not able to tackle drug development before because we did not know enough about the pharmaceutical field. We have found that it is a very demanding area that requires high levels of expertise to carry out drug development in the right manner.


Through the Scholar-Innovator grant's pilot funding, we were able to get our work up and running, and then the Harrington Discovery Institute's panel of industry experts have been able to lead us step-by-step through the process of creating a new drug. The Harrington Discovery Institute's support has also influenced the way we think as we were given a roadmap to move a lab bench experiment and turn it into a drug people can use.


Through your research you have raised awareness about colon cancer and high mortality rates associated with it. Has this influenced the behavior of patients you work with currently?


We are seeing more screenings for colon cancer and death rates from it are going down. There are still a lot of people who are not being screened; however, we hope that DNA-based testing will make a difference in bridging that gap. We developed the first stool DNA test, ColonSure, that also served as a basis for a biotech company to develop a successor test, Cologuard, that is now FDA-approved. Our SPORE has an important project being led by Gregory Cooper, MD, and Li Li, MD, that examines the situation of patients who have a positive stool DNA test but a normal colonoscopy. We are bringing these patients back a year later for repeated colonoscopy to test if they had tumors that were missed or have developed since the first exam. We are also working on developing molecular blood tests that can be used after a patient had surgery for colon cancer to be able to tell if a surgeon was able to remove the tumor entirely. In addition, we want to use a blood test for patients after surgery to be able to catch if the disease is coming back early on when it could potentially be removed. We couldn't have done this research without the support of our patients who in the midst of personal adversity are finding it in their hearts to participate in our clinical trials. We feel a real bond and commitment to our patients who let us study their blood, tissue, or undergo brushing in order to prevent and treat this disease.


An important additional new development is that patients and their families are now establishing funds to support research aimed at curing colon cancer. Two years ago a math teacher from Orange High School, Alla Bogomolnaya, succumbed to a rare form of colon cancer, signet ring adenocarcinoma of the colon. The Bogomolnaya family has now established the Alla Bogomolnaya Fund for Colon Cancer Research at University Hospitals. This was one of the first patient-driven funds to study the prevention and treatment of signet ring colon cancer. This memorial fund not only jump started the study of the genetics of the disease, but also created a national awareness and community for families who encountered this disease. We are witnessing that people who have personal experience with signet ring colon cancer are making donations to help us fight the disease. This is very moving and makes us feel that we have a tremendous personal commitment to people and families who have been affected by the disease.


You were the Howard Hughes Medical Institute (HHMI) investigator for 12 years. Do you miss this environment? Do you believe that HHMI takes on a different level of importance given the difficult situation with NIH funding currently?


The HHMI was very generous for supporting us for 12 years and we are certainly very grateful for that. We have replaced a good portion of the HHMI support with funding from SPORE and other NIH-funding mechanisms. We currently have support from three large-scale NIH-funding programs: the Barrett's Esophagus Translational Research Network (led by Amitabh Chak, MD), GI SPORE and NIH Early Detection Research Network (both led by me). The advantages of HHMI support were both the level of the funding and the freedom presented to investigators to use it in whatever way they deemed best. NIH funding is more directed and, therefore, not as flexible in supporting quick responses to new opportunities. Securing NIH support also requires a lot of time and effort in putting these grant proposals together. For example, our SPORE grant was over 1,000 pages long. As NIH funding levels have dropped precipitously, and the chance of receiving an NIH grant becoming less than 1/10, it means that an ever increasing percentage of time is taken up in procuring funding. We are at a point now where the amount of time that has to be invested to secure funding impedes the progress of bringing new discoveries to patients. Hopefully, the community of patients and families will work through the political process to convince the federal government to make budgetary investments in medical research. A dollar spent on medical research yields high returns from the extended life span and increased productivity that health brings. Medical funding has been steadily shrinking for over a decade now, and if this trend continues, we are faced with potential irreversible losses, where labs are closed, research teams are disbanded, and knowledge and expertise built up over decades disappear. This is heartbreaking to see, as it would take decades to rebuild.


You have held a number of leadership roles in national medical organizations. How do you see cancer research progressing over the next few years?


Researchers have established a dictionary of cancer; we know what makes this disease happen; we are at a point now to develop drugs that specifically target the molecular defects in cancers and individualize therapy for people. We want to be able to use the knowledge of molecular defects in cancer to come up with ways to detect it early when it is still curable as well as develop medications that will be able to prevent cancer. For example, one of the contributions that we made last year was the development of a test that could tell who would benefit from taking aspirin for preventing colon cancer. We've known for a long time that if you give aspirin to people, you will lower the number of patients with colon cancer; however, we have not particularly advocated individuals do so because we also know that a certain number of those people would develop stomach ulcers. Through our research we were able to show that aspirin prevents cancer only in individuals whose colons show a very specific molecular target and a patient can have a simple test of the colon to detect if taking aspirin would be beneficial. This is just one example of smart medicine that I hope to see more of. Ultimately, we have to understand why different individuals are susceptible to different kinds of cancers; this will suggest the changes of diet, lifestyle and medicine to help cut down their risk of developing cancer.


Schedule a clinical appointment with Sanford Markowitz, MD, PhD

Learn more about Dr. Markowitz's research and ways you can help

The department news report

Division of Cardiovascular Medicine

Marco Costa, MD, PhD, was selected to lead the Executive Office of Innovation as a Vice President and Chief Innovation Officer of University Hospitals. Dr. Costa will lead a team of professionals pursuing initiatives to maximize quality, patient experience and performance by building a culture of innovation.





Mukesh Jain, MD, FAHA, was selected for the 2015 North American Vascular Biology Organization (NAVBO) Judah Folkman Award in Vascular Biology. The award celebrates Dr. Jain's innovative and groundbreaking research accomplishments in the field of vascular biology.





Daniel Simon, MD, and Hiram Bezerra, MD, PhD, were the first physicians to use HeartFlow FFRCT for treating coronary artery disease in the United States. FFRCT is a new, noninvasive imaging technology for coronary artery disease designed to help physicians develop the right treatment plan for each patient. The new technology provides insight on the extent of the blockage and whether it is impacting blood flow to the heart, determining an individualized course of action for a patient.


Schedule a clinical appointment with Cardiovascular Medicine physicians





Division of Gastroenterology & Liver Disease

Fabio Cominelli, MD The work of Fabio Cominelli, MD, PhD, exploring the pathogenesis of Crohn's disease was highlighted in the International Innovation Journal. Dr. Cominelli argues that stimulation of the intestinal innate immune system, rather than its suppression, is beneficial in preventing and treating early Crohn's disease. Dr. Cominelli's team is currently developing novel therapeutic modalities based on NOD2 gene and probiotics to accomplish this goal.


Division of Geriatrics & Palliative Care

The work of Stefan Gravenstein, MD, MPH, entitled

"Association of Dementia with Early Rehospitalization among Medicare Beneficiaries" was highlighted by the Agency for Healthcare Research and Quality (AHRQ). In the article, Dr. Gravenstein and his team show that hospitalization of patients with a dementia diagnosis is more likely to be followed by a readmission within 30 days, compared to hospitalization of those without dementia.

In addition, Dr. Gravenstein's article entitled "A Qualitative Study of Choosing Home Health Care after Hospitalization: The Unintended Consequences of 'Patient Choice' Requirements" was published in the Journal of General Internal Medicine. In the article, the authors argue that upon discharge from the hospital, patients and their families rarely see state or federal quality reports about home health agencies. It is advised that Medicare and states consider actively marketing the reports to the case managers who help patients with discharge planning.


Schedule a clinical appointment with Geriatrics & Palliative Care physicians







Division of Hematology & Oncology

Sanford Markowitz, MD, PhD, identified new gene mutations unique to colon cancers in African-Americans. The article entitled "Novel Recurrently Mutated Genes in African-American Colon Cancers" was published in the Proceedings of the National Academy of Sciences Journal. Dr. Markowitz is working on developing treatments targeting the distinct nature of the disease that yield high incidence and death rates among African-American population.

An educational program about clinical trials for patients originally developed by Neal Meropol, MD, is now available via www.cancer.net, an award-winning patient information website of the American Society of Clinical Oncology (ASCO). The video-based program, called Preparatory Education About Clinical Trials (PRE-ACT), is designed to help patients learn more about clinical trials and address common misconceptions associated with participating in them. For many years Dr. Meropol has been focusing his efforts on increasing patient participation in clinical trials through improving patients' knowledge and attitudes through effective doctor-patient communication and education of patients and their families.The new tool offers a survey and then presents a series of videos that can help patients and their loved ones understand such topics as placebo, side effects, financial coverage and others to make informed decisions about health care and participation in clinical trials.

Institute for Transformative Molecular Medicine

Jonathan Stamler, MD, discovered that the molecule known as coenzyme A plays a key role in cell metabolism by regulating the actions of nitric oxide. Dr. Stamler's findings were published in the article entitled "Identification of S-Nitroso-CoA Reductases that Regulate Protein S-Nitrosylation" in the Proceedings of the National Academy of Sciences. Dr. Stamler's team also found new enzymes that regulate nitrosylation by coenzyme A. The newly discovered classes of enzymes provide entry into metabolic regulation in mammals and offer new pathways for understanding and regulating cell metabolism.

department conferences & events

Grand Rounds

When: Tuesdays, 12:00 - 1:00 p.m.

Where: Kulas Auditorium, Lakeside, 5th Floor


February 3

"Is Hot Spotting Spot On? Lessons Learned from Implementing a Program to Address High Utilizers" by Brook Watts, MD


February 10

"Diagnosis, Classification and New Treatments for Lymphoma" by Paolo Caimi, MD


February 17

"Innovation" by Marco Costa, MD, PhD


February 24

"Pandora's Box: Who Gets to Open? Advancing Hospitalized Elderly Care Through Recognition and Coalition" by Gowrishankar Gnanasekaran, MD, MPH

department humanities journal

Lasting Impressions is an online medical humanities journal that serves as an avenue for artistic expression of the Cleveland medical community. It is an outlet for providers to share their reflections on anything from patient interactions to work/life balance. By sharing our lives through artwork and writing, our medical experience is elevated, and our medical community becomes stronger.

Submission Guidelines

What: Poetry, prose, photography or artwork from medical students, trainees, alumni, faculty and health care workers

Deadline: March 1, 2015

Contact: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Detailed Guidelines

department leadership council minutes

Leadership Council

Dr. Walsh updated council members on the following Chair searches: Department of Urology, Search Committee chaired by Dr. Cliff Megerian; and Department of Surgery, Search Committee chaired by Dr. Warren Selman.


Leadership Council

Dr. Walsh led a discussion with council members regarding the re-affiliation agreement between Case Western Reserve University and University Hospitals Case Medical Center.

Among the nation's leading academic medical centers, University Hospitals Case Medical Center is the primary affiliate of Case Western Reserve University School of Medicine, a nationally recognized leader in medical research and education.