Ten New Members Join DF/HCC
Ten individuals from our seven member institutions have recently joined DF/HCC. See below to learn more about these scientists and their research interests.
Paul Anderson, MD, PhD (HMS)
Research focus: the post-transcriptional mechanisms that regulate the production of inflammatory mediators. Many mRNAs that encode inflammatory mediators possess adenine and uridine-rich elements (AREs) in their 3’ untranslated regions that inhibit translation and promote mRNA decay. The regulated activity of ARE-binding proteins (ARE-BPs) is required to overcome constitutive translational repression and mRNA instability. TIA-1, TIAR and TTP are ARE-BPs that prevent the pathological overexpression of inflammatory mediators. Both TIA-1 and TTP regulate the assembly of cytoplasmic stress granules, discrete foci at which untranslated mRNAs accumulate in stressed cells. Stress-induced phosphorylation of the translation initiation factor eIF2a allows TIA-1 to promote the assembly of untranslated, non-canonical 48S preinitiation complexes that are the core constituents of stress granules. Research interests include the idea that stress granules function as sites of mRNA triage: by monitoring the composition and function of mRNP complexes, the stress granule determines whether individual mRNAs are stored, degraded, or re-initiated.
Nathanael Gray, PhD (DFCI)
Research focus: how small molecule inhibitors with selectivity toward a desired wild-type or drug-resistant kinase can be efficiently developed, how to use kinase inhibitors to dissect the molecular wiring of signaling pathways, what the most efficient ways to develop small molecule modulators for protein targets are for which no ligand is currently known, how to develop a small molecule modulator for biological pathways for which very little is known, and developing new methods for identifying the biological targets for small molecules of unknown mechanism.
Bernhard Kuhn, MD (CHB)
Elena Levantini, PhD (BIDMC)
Research focus: the molecular pathogenesis of lung cancer. Interests include exploring the effects of C/EBPα down-regulation in experimental models of lung cancer and tobacco-damaged epithelium, using inducible models of lung-specific C/EBPα deletion, and analyzing the differentiation and self-renewal capabilities of C/EBPα-deleted pulmonary stem cells in order to gain knowledge on the molecular mechanisms that C/EBPα is orchestrating in lung stem cells. Characterization of critical regulatory mechanisms governed by the master regulator C/EBPα as well as the aberrant differentiation pathways in C/EBPα-deleted pulmonary stem cells would be of critical relevance for understanding the pathogenesis and identification of novel treatment targets for tobacco-related lung diseases.
Rebecca Miksad, MPH, MD (BIDMC)
Research focus: current and recent research projects include: 1) validation of progression-free-survival as a surrogate endpoint for overall survival in advanced breast cancer; 2) markov model decision analysis of bisphosphonate treatment; 3) quality of life (QoL) phone survey of cancer patients with osteonecrosis of the jaw using disease-specific and generic health related QoL instruments; 4) development of a protocol to assess the efficacy of neoadjuvant sorafenib for radiofrequency ablation of localized hepatocellular carcinoma; 5) analysis of SEER-Medicare insurance/HMO enrollment/disenrollment for cancer patients; 6) prostate cancer QoL for patients undergoing active surveillance; 7) internet based QoL assessment; and 8) value of targeted chemotherapeutics
Pier Paolo Pandolfi, MD, PhD (BIDMC)
Research focus: elucidating the molecular mechanisms and genetics underlying the pathogenesis of leukemias, lymphomas, and solid tumors as well as modeling these cancers in the mouse. Past works has included the characterization of the function of the fusion oncoproteins and the genes involved in the chromosomal translocations of acute promyelocytic leukemia (APL), as well as of major tumor suppressors such PTEN and p53 and novel proto-oncogenes such as POKEMON. The elucidation of the molecular basis underlying APL pathogenesis has led to the development of novel and effective therapeutic strategies. As a result of these efforts, APL is now considered a curable disease. Novel therapeutic concepts that have emerged from this work are currently being tested in clinical trials.
Deborah Schrag, MPH, MD (DFCI)
Research focus: cancer care delivery, especially in the area of colorectal cancer, including the patterns and outcomes of cancer treatment in order to determine how well treatments with efficacy established in the clinical trial setting are translated into practice in non-research settings. Recent work includes technology diffusion and efforts to identify what determines how rapidly new treatments are adopted and the factors that drive utilization. Current projects include evaluating the quality of care delivered to indigent patients with cancer who are insured by State Medicaid programs in New York and California. Other interests include improving the cancer care experience for patients by enhancing data collection, information systems, and ultimately patient-clinician communication. In addition, I am interested in evaluating the extent to which individually tailored patient information such as the preparation of treatment summaries and treatment plans serve to enhance care coordination and quality.
Rob van Dam, PhD (HSPH)
Research focus: evaluating the role of diet and genetic factors in the development of obesity and type 2 diabetes. Because these and related conditions, such as hyperinsulinemia, are increasingly recognized as important determinants of various types of cancer this research is directly relevant for cancer etiology. Additional research interests include the study of dietary patterns in relation to risk of cancer. Research methods include prospective cohort studies, dietary intervention studies, and meta-analyses. Currently, specific topics of interest include the health effects of coffee and dietary phenols and the interaction between genetic characteristics (copy number variants, genome-wide association studies) and dietary factors.
David Weinstock, MD (DFCI)
David Williams, MD (CHB)
Research focus: the biology of hematopoietic stem cells, specifically the understanding of the interaction of hematopoietic stem cells with the bone marrow and the abnormalities of these interactions which are associated with leukemia. These basic studies contribute to translational research that utilizes hematopoietic stem cells as a target for gene therapy manipulations. Interests include the Rho family of small GTPases, members of the Ras superfamily. The best studied members of this family are Rac1, RhoA and Cdc42. Past studies include utilizing gene-targeted mice lacking Rac GTPases to show that Rac is critical for the development and evolution of the myeloproliferative disease associated with expression of the p210 Bcr-abl oncogene. These studies have led to the testing of a small molecule inhibitor of Rac on primary CML samples and in the mouse model. Additional interests include studying the potential role of other GTPases in acute myeloid leukemia and chronic. These studies examine primary samples and leukemia cell lines and are specifically examining the role of Rac and another GTPase, called RhoH, in the leukemia cell phenotype.