Four P&S Physician-Scientists Named 2014 Irving Scholars

The Irving Institute for Clinical and Translational Research announced four young clinical investigators as 2014 Irving Scholars, who will conduct research to improve treatments for blood cancer, depression, obsessive-compulsive disorder, and antibiotic-resistant infections. Each researcher will receive a three-year career development award and named professorship.

Since 1987, the Irving Scholars program has provided more than $16 million in support to 112 of Columbia's most promising young clinical investigators.

The 2014 Irving Scholars are: Siddhartha Mukhejee, MD, DPhil, Medicine-Oncology; Carolyn Rodriguez, MD, PhD, Psychiatry; Bret R. Rutherford, MD, Psychiatry; and Anne-Catrin Uhlemann, MD, Medicine-Infectious Diseases. Short descriptions of their project proposals appear below.

The Irving Institute is part of the NIH Clinical and Translational Science Award (CTSA) consortium of 62 U.S. academic medical centers. The focus of the Irving Institute is to transform how clinical and translational research is conducted, enabling medical investigators to develop new treatments faster—and to deliver those treatments to patients more efficiently and more effectively.

Siddhartha Mukherjee, Herbert Irving Assistant Professor of Medicine “Predicting the Responsiveness to a Novel Multi-Kinase Inhibitor in Patients with Low–Risk Myelodysplastic Syndrome”

Therapeutic options for a group of blood disorders called myelodysplasic syndromes remain limited, especially for types with a lower risk of developing into leukemia.

Though therapeutic options for patients with low-risk MDS exist, they are of limited value, as resistance develops rapidly.

After testing a new multi-kinase inhibitor, rigosertib, in patients with many different types of MDS, Dr. Mukherjee found that the drug was particularly effective in patients with a type of low-risk MDS called RARS (for refractory anemia with ringed sideroblasts).

An impressive number of RARS patients in the trials—40 to 50 percent—responded to the drug, but researchers do not know how the drug works or why it works only in some patients.

Dr. Mukherjee’s project will look for genetic markers that predict response to the therapy and use these to select patients for future phase III clinical trials of the drug.

Carolyn Rodriguez, MD, PhD, Florence Irving Assistant Professor of Psychiatry “Mechanisms of a Novel Treatment Target for Mental Illness”

Dr. Rodriguez will continue her pioneering research that has identified a potential new way to rapidly reduce symptoms of obsessive-compulsive disorder (OCD).

Current drugs for OCD take months to work, do not work in all patients, and often provide only limited relief from symptoms. Based on evidence that the glutamate system is involved in OCD, Dr. Rodriguez tested a drug that blocks the glutamate receptor NMDA.

She discovered that a single IV infusion of ketamine immediately reduces obsessive thoughts in people with OCD and that the effect can last for more than a week. These results have generated excitement among researchers (the data was presented at a “Hot Topics” panel at the American College of Neuropsychopharmacology meeting) and patients.

Dr. Rodriguez will continue to investigate how the drug changes the brain to alleviate OCD symptoms, so that compounds with fewer side effects can be identified.

Bret R. Rutherford, Herbert Irving Assistant Professor of Psychiatry “Dopaminergic and Opioid Mechanisms of Placebo Effects in Major Depression”

In studies of pain relief, researchers have found that if people believe a therapy, including a placebo, will lessen pain, natural opiates in the brain are released and cause measurable decreases in pain.

Relief from depression is also subject to a patient’s beliefs, but it is unclear why.

Dr. Rutherford’s project will investigate whether the mechanism underlying the placebo effect in pain also causes placebo responses in major depression.

Understanding the neurobiology of placebo effects in major depression may lead to ways to reduce or increase the placebo effect when desired. Minimizing placebo response in clinical trials would aid the evaluation of new antidepressant medications, while maximizing the response in patients would optimize currently available treatments.

Anne-Catrin Uhlemann, Florence Irving Assistant Professor of Medicine “Risk Factors for Carbapenemase-resistant Klebsiella Pneumonia Infection in Liver Transplant Patients”

In 2013, the CDC Threat Report named carbapenem-resistant Klebsiella pneumoniae (CRKP) as one of the three most urgent bacterial threats to modern health care.

Carbapenems are considered antibiotics of last resort, and carbapenem-resistant infections are associated with high morbidity and mortality that often exceeds 50 percent.

No other group of patients has been found to have a higher life-threatening risk from these infections than recipients of liver transplants. Recent studies have indicated that reservoirs of CRKP in the intestinal track of these patients can lead to infection and contribute to transmission across the hospital.

Dr. Uhlemann, with the help of the New York Genome Center, will look for molecular and microbiological risk factors of CRKP infection in patients undergoing liver transplantation and assess how they contribute to hospitalwide outbreaks. As novel treatment strategies are lacking, efforts to identify, contain, and limit the dissemination of carbapenem-resistant bacteria are paramount to controlling this epidemic.


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