Donaghue Investigators: An Update

The Donaghue Investigator program provided over $16 million to 27 medical researchers holding faculty appointments at Connecticut institutions between 1998 and 2012. Goals of the program included supporting the overall work of the researcher rather than a single research project, funding research in a broad array of medical research fields, and looking for the potential for
practical benefit to improve health high on the list of priorities for selecting awardees. This is the third in a series of articles to revisit the Donaghue Investigator program. We asked each of our grantees to share with us some highlights from their current work, and here is what seven of them had to say. Twelve Donaghue Investigators were featured in the previous Practically Speaking, and we’ll hear from others in upcoming issues.

2000

Nancy M. Petry, PhD
Professor of Medicine, University of
Connecticut School of Medicine

“Brief Intervention for Problem Gamblers”

Develop and test brief interventions to reduce gambling problems

I am thankful to have received the five-year Donaghue Investigator Award for supporting my interests in behavioral addictions before any funding was available from the National Institutes of Health in this area. This award provided initial data that sparked several subsequent awards funded by the NIH and work that I am continuing to this day. The interventions I designed and initially tested through the Donaghue Award are now being applied clinically to treat patients with gambling disorder, including those with co-occurring substance use and gambling disorders. I have published over 100 papers on gambling disorder and its treatment as well as a book on the condition. My research in this area is now extending to other behavioral addictions as well, including Internet gaming problems in youth and young adults.

1999

Stephen L Helfand, MD
Professor of Biology
Brown University

“Molecular genetics of aging”

Elucidating the molecular genetic basic of aging and mutations in specific genes that extend life span.

Funding from the Donaghue Foundation initiated our studies on the molecular genetics of aging leading to the discovery of one of the first longevity genes in the fruitfly, the Indy (I’m not dead yet) gene. Reducing Indy activity by genetic or pharmacologic methods mimics the positive effects of calorie restriction in flies and mice without the need to restrict calories, and effectively treats Type 2 diabetes, non-alcoholic fatty liver disease, obesity and age-related hypertension in mice. Investigation of the molecular underpinnings of calorie restriction led to our demonstrating the importance of Sirtuins in calorie restriction, and the discovery of the small molecule activator, resveratrol, that extends healthy life span in flies and mice. Donaghue funding has provided the essential resources to show that using molecular genetic and pharmacological tools it is possible, and even practical, to delay age-related effects of the metabolic syndrome and extend healthy life span in humans.

2002

Kevin P. Claffey, PhD
Professor of Cell Biology
University of Connecticut School of Medicine

“Mechanisms of MT1-MMP-dependent breast cancer metastasis”

Studying molecular mechanisms related to tumor growth and metastasis

The Donaghue Investigator award allowed us to initiate a breast tumor tissue bank to study the activation of invasive enzymes that promoted invasion and metastasis. While we were banking tissues, we discovered that tumor-draining lymph nodes were producing immune reactions to the cancer, thus identifying unique antigens in their cancer. We were awarded two competitive national grants, NIH:NCI IMAT and a DOD IDEA award to recover anti-cancer antibodies in patient-derived tumor-draining lymph nodes. To this end we have identified a very unique antibody that recognizes the cell surface of only aggressive breast cancer that surprisingly also targets high grade ovarian, melanoma, lung and bladder cancers! Current work aims to translate this finding into novel immunotherapy applications for lethal metastatic cancers for which effective therapies are lacking. We are hopeful that we can eventually add to the arsenal of treatments to cure not only breast cancer but multiple other cancers as well. Donaghue resources supported our interactive translational science involving Clinicians, Scientists, Nursing and Administrative staff as well as a unique and rewarding interaction with Patients, all dedicated towards better outcomes for future cancer
patients.

2008

William Zempsky, MD
Division Head, Pain and Palliative Medicine
Connecticut Children’s Medical Center
Professor of Pediatrics
University of Connecticut School of Medicine

“Sickle Cell Pain: A novel approach to assessment and relief”

New ways to treat pain in children with sickle cell disease

The Donaghue Investigators grant was instrumental in advancing my career and research in pain in sickle cell disease. It set me on a ten year path of research, clinical care and advocacy. Due to the work supported by Donaghue, I have been able to obtain two major NIH grants, a K23 career development award, and last year an R01 grant to develop and evaluate a web based intervention to improve coping abilities for youth with sickle cell disease and pain. I have published on a wide variety of topics in the field including the development of new assessment tools, functional imaging findings and chronic pain in sickle cell disease. My commentary in JAMA regarding the inadequate treatment of individuals with sickle cell disease has been at the forefront of efforts to improve care in the emergency department. My ongoing work will enhance the lives of individuals with sickle cell while helping understand the transition to chronic
pain in this disease.

1999

Carlos M. Grilo, MD
Professor of Psychology and Psychiatry
Yale School of Medicine

“Treatment of binge eating and obesity”

Development of clinical treatment programs for obesity

The Donaghue Investigator Award provided an invaluable opportunity to pursue a series of interrelated treatment studies for persons with obesity and disordered eating. The award, which came at a critical point in my professional career, supported rigorous controlled treatment research aimed at identifying effective methods for persons with eating/weight disorders. Importantly, the award allowed and fostered innovation and risk taking in pursuing clinical advances. Our research program moved treatment research from “efficacy” towards “effectiveness” studies by performing studies in diverse generalist and community-based settings. In one direction, we developed and tested “scalable” methods critical to addressing the major gap in dissemination research and ethnic or racial health disparities with eating/weight disorders. In the other direction, we developed “adaptive and SMART” treatment approaches for addressing the needs of refractory and complex patients with multiple needs. We have sustained our commitment to integrating training into our research program with the view towards mentoring the next generation of independent and productive clinical-researchers needed to address this major public health problem.