Professor of Pathology; Director of Pathology Tissue Services; Director of Translational Pathology
Dr. David Rimm, is a Professor in the Department of Pathology at the Yale University School of Medicine. He completed an MD-PhD at Johns Hopkins University Medical School followed by a Pathology Residency at Yale and a Cytopathology Fellowship at the Medical College of Virginia. He is board certified in Anatomic Pathology and Cytopathology. At Yale since 1994, Dr. Rimm is the Director of Yale Pathology Tissue Services and the Yale Tissue Microarray Facility. He is a member of the Executive...
Dr. David Rimm, is a Professor in the Department of Pathology at the Yale University School of Medicine. He completed an MD-PhD at Johns Hopkins University Medical School followed by a Pathology Residency at Yale and a Cytopathology Fellowship at the Medical College of Virginia. He is board certified in Anatomic Pathology and Cytopathology. At Yale since 1994, Dr. Rimm is the Director of Yale Pathology Tissue Services and the Yale Tissue Microarray Facility. He is a member of the Executive Team in Pathology and serves as the Director of Translational Pathology. His lab group (15 researchers) focuses on quantitative pathology using the AQUA® technology invented in his lab with projects related to predicting response to therapy in breast cancer and predicting recurrence or metastasis in melanoma and lung cancer. He is currently supported by 9 grants from both public and private sources. He serves as a reviewer for the NIH and was a charter member of the Cancer Biomarkers Study Section. He is an editorial board member for 7 pathology journals and a member of the pathology committee for TransALLTO and TEACH (cooperative groups or therapeutic clinical trials). He is an author of over 275 peer-reviewed papers and 8 patents and was the scientific co-founder of HistoRx, a digital pathology company (sold to Genoptix in 2012) and Metamark Genetics, a prognostic determinant company.
Associate Research Scientists
Seema Agarwal, PhD (Org Chem), PhD (Bio)
BS, Allahabad University (1982)
MSc, Allahabad University (1984)
PhD, Allahabad University (1990)
PhD, Lehigh University (1995)
Next generation cell line model systems for cancer and identification of novel biomarkers for metastasis.
As a career research scientist, I have made efforts to diversify my basic science portfolio. I have worked extensively in organic synthesis, biochemistry, genetics, genomics, molecular and cellular biology in order to gain the comprehensive understanding of complex diseases like cancer. One of my interests is in finding a way to identify different signaling pathways that contribute in cancer growth and metastasis and to develop drug combination therapies. Another field of interest is to quantitatively measure proteins in clinical samples and to identify novel biomarkers for identifying patients that will be at high risk of developing metastasis as well as biomarkers that will be useful in identifying patients that will be either resistant or sensitive to a given treatment regimen. I have also developed two methods to culture primary tumors with an ultimate goal of recapitulating primary human cancers to better understand the biology of cancer initiation, progression and metastasis; identify novel drug targets; de novo and acquired resistance to drugs, to utilize these systems to identify novel drug combination for personalized medicine concept/approach. First method involves growth of cancer cells in 3D directly from biopsy or FNA samples from breast cancer patients that are enriched in stem cell like properties. Second method is to grow, expand and maintain primary cell cultures derived directly from patient's tissues samples (biopsies and FNAs) using feeder cells and ROCK inhibitor.
MD, PhD, Beijing Medical University, Beijing, China
Human tissue, collected by physicians for diagnostic purposes, is an extremely valuable resource for translational research. As a team member of YPTS, I am currently working on providing high quality annotated fresh, frozen and formalin-fixed, paraffin-embedded human tissue to Yale and other users, to maximize the access of human tissues to translational investigators.
In situ measurement of tissue biomarkers for companion diagnostics in cancer
I trained as a cell biologist and surgical pathologist. My research is focused on measuring tissue biomarkers, including proteins and nucleic acids, and testing their potential for use as companion diagnostics in cancer. I am currently working on the in situ measurement of diverse protein targets and mRNA transcripts in human breast and lung carcinoma samples using automated quantitative fluorescence and novel RNA hybridization techniques. These methods provide increased sensitivity, specificity and reproducibility. More quantitative approaches could open new opportunities for biomarker discovery and patient selection for anti-cancer treatments, an essential component of personalized cancer medicine.
BS, Biology, Fairfield University
PhD, Biochemistry and Molecular Biology, Thomas Jefferson University
Defining a Molecular Signature for Melanoma Recurrence and Standardization for QIF
Melanoma patients that are sentinel lymph node negative are generally not treated with adjuvant therapy due to their toxicities. However, a number of these patients will experience recurrence and ultimately succumb to the disease. Our goal is to improve a molecular signature that we developed to identify sentinel lymph node negative melanoma patients most at risk for disease recurrence and therefore, would benefit from adjuvant or more aggressive therapy. I am also working on a project to develop better controls and standards for quantitative immunofluorescence (QIF).
My training as a surgical pathologist led me to understand the importance of translational research on patient care. My current effort is focused on the development and validation of quantitative in situ protein assays for tissue biomarker measurement in lung and breast cancer. Quantification of these markers could provide important prognostic/predictive information and support the use of novel targeted therapies. I'm also interested in the mechanisms used by tumor cells to exert their influence over the adaptive immune system and downregulate T cell responses. Another focus of my work has been the reassessment and selection of tumor samples and controls for cancer genome sequencing.
Residents & Fellows
PGY-6 Hematology/Oncology Fellow
Evasion of the Anti-tumor Immune Response: Prognostic and Predictive Biomarkers in Lung Cancer
Despite recent advances in therapies for lung cancer, advanced cases continue to have poor overall survival. Recently, therapies directed at the immune inhibitory pathway of the PD-1/PD-L1 axis have shown activity in lung cancer. My research focuses on the expression of molecules thought to be involved in evasion of the anti-tumor immune response in lung cancer. Expression of these molecules will then be correlated to variables such as overall survival and response to therapies, such as those currently directed at the PD-1/PD-L1 axis. Biomarkers that predict response to anti-PD-1/anti-PD-L1 therapies can help direct patient care regarding potential therapeutic options.
Graduate Students (PhD and MD/PhD)
Hallie Wimberly, PhD Candidate, Experimental Pathology
BS, Microbiology, University of Texas
Estrogen receptor beta and alternatively spliced variants in estrogen signaling and relevance to clinical response to endocrine therapy
Estrogen receptor (ER) alpha is not the only mediator of estrogen signaling. Other ER isoforms and alternatively spliced variants may be crucial in mediating cellular response to estrogen and may provide insight into sensitivity to endocrine therapy in breast cancer patients. However the current literature is riddled with conflicting results and opinions on whether or not ERbeta is a useful biomarker. I aim to investigate the significance of ERbeta variants in the clinical setting by examining correlations of their expression with patient survival and response to therapy by measuring expression with rigorously validated antibodies using quantitative immunofluorescence.
BS, Duke University, Chemistry
Determining Biomarkers that Predict Response to Neoadjuvant Chemotherapy in Breast Cancer
For locally advanced breast cancers, neoadjuvant chemotherapy is often administered prior to surgical intervention. Despite its value in facilitating breast conserving surgery, this treatment modality does not improve overall survival compared to adjuvant chemotherapy. Biomarkers that predict response to therapy can better guide treatment strategy and avoid adverse effects from cytotoxic chemotherapy. My research aims to establish a quantitative immunofluorescence-based molecular signature that predicts whether a breast tumor will respond to neoadjuvant chemotherapy.
Lauren Moore, PhD Candidate, Pharmacology
Investigation of Molecular Mechanisms that Govern Taxane Resistance
The clinical application of biomarkers has greatly reduced the mortality rates associated with breast cancer; however, there is an urgent need for the identification and validation of novel biomarkers that can more effectively predict response to taxane chemotherapy. My project focuses on identifying molecular targets that may play a role in molecular mechanism of taxane resistance primarily through a combination of screening and in vitro cell based-assays. The objective of this research is to elucidate the mechanisms that govern resistance and to identify potential biomarkers that may have predictive and prognostic abilities for breast cancer.