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 placing the potential for practical benefit to improve health high on the list of priorities for selecting awardees. This is the first of a four-part series 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 six of them had to say. We’ll feature the other Donaghue Investigators in future Practically Speaking issues.
David L. Rimm, MD, PhD
Professor of Pathology and Medicine
Yale School of Medicine
1998 Donaghue Investigator award “Adhesion protein expression as mechanism to predict metastasis”
The two Donaghue awards (the earlier award was from the New Investigators program) were critical in the early stages of my career. Both were focused on the translation of biomarkers from basic concepts to clinical tests that affect patient care. At the time, my work was mostly focused on breast cancer, and the work we did with Donaghue funding helped us understand key issues of standardization of measurement of biomarkers on tissue slides. That work was the precursor to many subsequent studies in my lab related to more quantitative analysis of biomarkers, first in breast cancer, and now in melanoma and lung cancer as well. We have now published over 200 papers using concepts and methods developed in conjunction with the Donaghue funding. Some of these works have begun to change patient care. Currently, we are working on validation of a new assay for HER2 in breast cancer and a number of assays for immune-oncology. Also, we are working closely with the FDA on a new method for standardizing assays for companion diagnostic testing that is likely to become a requirement for agency approval of some diagnostic tests. At the time, I believe one of the goals of the Donaghue Investigator program was “impact.” I think we have succeeded.
Lisa Dierker, PhD
Professor of Psychology, Wesleyan University
2003 Donaghue Investigator award “Impact of child psychopathology and interventions on later substance use”
I continue to conduct research on the addiction process in youth and the role of mental health symptoms in exacerbating risk for the development of substance abuse and dependence, by employing promising, new quantitative methods with the goal of informing the content and timing of intervention. Unexpectedly, my work with mental health and addiction communities in Connecticut during the Donaghue Investigator Award also sparked in me a new passion for introducing a wider and more diverse audience to the skills needed to ask and answer the most challenging and important questions we face today. Through funding from the National Science Foundation and in partnership with the Department of Education’s GEAR UP program, I am currently disseminating a welcoming, project-based model for teaching data analysis and applied statistics not only to college students, but to youth as early as grade 9. A video of this program and the students who have participated is at http://passiondrivenstatistics.com/2016/09/21/gear-up.
Stephen M. Strittmatter, MD, PhD
Vincent Coates Professor of Neurology and Professor of Neuroscience
Yale School of Medicine
1998 Donaghue Investigator award “Axonal regeneration after spinal cord injury’
Many neurological conditions disrupt connections between neurons. The regeneration of axons has the potential to provide functional neurological recovery, without requiring “new” cells. Unfortunately, the brain and spinal cord of adult mammals has extremely limited capacity for axon regeneration. Our axonal growth studies discovered Nogo and Nogo Receptor (NgR1). We demonstrated their role in preventing axonal sprouting, regeneration and recovery after spinal cord injury. We developed an NgR1 antagonist, which successfully promotes preclinical spinal cord recovery, even long after damage. Clinical trials are being prepared now.
While factors such as NgR1 are known, they provide an incomplete explanation for poor regeneration. Recently, we tested each and every gene for its ability to restrict axon repair in vitro and discovered many new regeneration factors. We are evaluating these novel genes using model organisms, biochemical methods and translational models of traumatic spinal cord injury in order to develop additional and more effective recovery therapies.
Becca R. Levy, PhD
Professor of Epidemiology, Yale School of Public Health
Professor of Psychology, Yale University
2006 Donaghue Investigator award “Promoting older individuals’ health through positive age beliefs”
I feel grateful to have received the five-year Donaghue Investigator Award, especially because it supported my research program as I started my first academic position. Previously, my research had been conducted experimentally; it demonstrated that positive age stereotypes can have a beneficial effect on older individuals’ health and functioning, whereas negative age stereotypes can have a pernicious effect. The Investigator Award provided the resources to transport this research by examining how age stereotypes, assimilated from the surrounding culture, can impact the health and functioning of older individuals living in the community. Building on the Investigator Award, we recently found that individuals with more-negative age stereotypes earlier in life are at greater risk of developing Alzheimer’s-disease biomarkers in later life. I look forward to continuing to build on my Investigator Award by comparing age-stereotype dynamics cross-culturally and developing ways to improve aging health by reducing negative age stereotypes and ageism.
Mark B. Gerstein, PhD
Albert L. Williams Professor of Biomedical Informatics
1998 Donaghue Investigator award “Analysis of gene sequences and protein structures”
My lab does research in bioinformatics, applying computational approaches to problems in molecular biology. Broadly, we are interested in large-scale analyses of genome sequences, macromolecular structures, and functional-genomics datasets. It is hoped that these will allow us to address a number of overall statistical questions about macromolecules, relating to their physical properties, cellular function, interactions, and phylogenetic distribution. We are especially focused on the human genome and proteome. Our research involves a number of quantitative techniques, including database design, systematic data mining and machine learning, visualization of high-dimensional data, and molecular simulation. More specifically, we focus on three questions. First, we are interested in annotating the raw human genome sequence, especially in characterizing the vast intergenic regions. Next, we are trying to get at the function of all the genes encoded by the genome. Here, we try to characterize function on a large-scale through the use of molecular networks. Finally, for the group of protein-coding genes that have known 3D structures, we are trying to see how their function is carried out through motion and how motion can be predicted from packing geometry.
Quing (Ching) Zhu
Professor of Biomedical Engineering and Radiology
2006 Donaghue Investigator award “Novel imaging devices for diagnosis and treatment of breast cancers”
With the Donaghue Investigator support from Donaghue Foundation, I have continued my research on improving breast cancer diagnosis using a hand-held ultrasound and diffused light imaging device and secured two rounds of NIH funding from 2007 to 2018 totaling more than $3M. The hand-held device and the system has been used on more than 450 patients and demonstrated its potential for significant reduction of benign breast biopsies. In addition, the device has also been used effectively in assessing patients’ response to neoadjuvant chemotherapy. I have also expanded my research to ovarian cancer diagnosis using ultrasound and photoacoustic imaging and received $1.6M from NIH from 2011 to 2017. I joined Washington University in St. Louis as a Professor of the Departments of Biomedical Engineering and Radiology in July 2016 and currently am continuing breast and ovarian cancer research and developing new technologies and exploring new applications for rectal and brain cancer research.