Pathology Research

Research Overview:

The Pathology Research group is focused on the development of novel diagnostic detection assays for Lyme disease and cancer.  In collaboration with the Danbury Hospital Department of Oncology, Department of Research and Innovation, Inc., our group is developing an assay based on Immunofluorescence using the RareCyte™ technology, to detect abnormal circulating plasma cells in peripheral blood, whose increasing numbers has been proven a major risk factor for progression of MGUS to MM.  This new methodology, which is more sensitive and less invasive than current detection methods, may enable better monitoring of disease status and help predict the subset of patients who are at greatest risk for progression of MGUS to MM.

Lyme disease, a systemic tick-borne infection caused by bacteria Borrelia burgdorferi, is the most common vector-borne disease in the USA. The current Centers for Disease Control and Prevention-approved diagnostic methods to detect Lyme disease are inaccurate in the early stages of the disease, as they rely on the detection of a host antibody response that often takes 3 weeks or more to develop. We are trying to develop a very sensitive and specific assay for an early direct detection of B. burgdorferi from blood of Lyme disease patients. A diagnostic test to directly measure B. burgdorferi in the blood would significantly enhance the detection of Lyme disease in the early stages, when treatment is most effective.

The Department of Pathology Research, in collaboration with Gastroenterology and Tumor Biology, is currently conducting a study that focuses on analysis of an individual’s gut microbiome DNA to characterize bacterial composition and prevalence as a possible indicator of CRC (colorectal cancer) risk.  DNA is extracted from stool samples and a bacterial profile is identified by next generation sequencing.  Trends in abundance and diversity are assessed and correlated with clinical and pathology data to assess whether there is a correlation between the abundance of bacterial species and CRC risk.

Research Training Internship

The Biomedical Research Institute offers a 4-week (24 hours/week) research program designed to introduce students to a variety of protocols and techniques used in research.  The program provides an opportunity for students to work with a senior scientist in order to learn or improve technical skills and obtain a basic understanding of the biomedical research field.  The program emphasizes hands on laboratory experience, where students spend a majority of their time learning research techniques, maintaining a research notebook and general laboratory upkeep.  Currently the program offers experience in pipetting accuracy, bacterial growth, protein lysis and quantitation, agarose gels, electrophoresis, western blot analysis, fluorescent microscopy, polymerase chain reaction (PCR) and enzyme-linked immunosorbent (ELISA) assays.  Based on student input and recommendations the program continues to evolve and expand in order to meet the ever changing direction of research.

Paul Fiedler

Personnel

Paul N. Fiedler, MD

Paul N. Fiedler, M.D. is Chair, Department of Pathology & Laboratory Medicine at the Western Connecticut Health Network. He also holds academic appointments at Yale University, the University of Vermont, and Ross University. With over 22 years of experience as an attending pathologist, medical educator and inventor of medical tests, Dr. Fiedler leads a team of highly skilled pathologists, scientists, pathology residents and medical technologists in providing laboratory services for patients in Western Connecticut and developing novel assays that have promising clinical applications. His research interests relate to the detection of rare cells in whole blood and the quantification of protein biomarkers in tissue utilizing newly invented technologies and methods. Dr. Fiedler has published over 80 papers and abstracts and has been granted 9 United States patents. He currently serves on the Practice Management Committee for the College of American Pathologists and is past-president of both the Connecticut Society of Pathologists and American Association for Clinical Chemistry, Connecticut Valley Section. In addition, Dr. Fiedler has provided consultative services to pharmaceutical and diagnostic companies and has served as expert witness in medical-legal proceedings.

Pathology

Denise McKibben, Ph.D., Manager Pathology Research

Donna Guralski, MS,  Lead Research Associate, Pathology

Lisa Arrigo, M.S., Pathology Research Associate

Jennifer Campbell, BS, HT(ASCP)cE

Grants

Direct visualization assay for detection of B. burgdorferi in early Lyme disease.  Award Number R43AI113990; August, 2014.  $600,000 grant from the National Institute of Allergy and Infectious Disease (NIAID) Small Business Innovation Research Program (SBIR) awarded to RareCyte, Inc. in collaboration with the Western Connecticut Biomedical Research Institute.

Publications

  • Pandya, D., Mariani, M., He, S., Andreoli, M., Spennato, M., Dowell-Martino, C., Fiedler, P., Ferlini, C. Epstein-Barr Virus microRNA expression increases aggressiveness of solid malignancies. PloS One. 2015; 10(9): 0136058.
  • Mariani, M., Karki, R., Spennato, M., Pandya, D., He, S., Andreoli, M., Fiedler, P., and  Ferlini, C.  Class III b-tubulin in Normal and Cancer Tissues. Gene, 2015, 563 (109-114). Synopsis published in Wikipedia (http://en.wikipedia.org/wiki/TUBB3), March, 2015.
  • Naddaf, E., Karnabi, E., Fiedler, P. Multifocal Inflammatory Pseudotumor of the Trigeminal Nerve and the Lung. Clinical Neurology and Neurosurgery, 2015, 128: 70-71.
  • Donato, M., Fanelli, M., Marian, M., Raspaglio,G., Pandya, D., He, S., Fiedler, P., Petrillo, M., Scambia, G., Ferlini, CNek6 and Hif-1α cooperate with the cytoskeletal gateway of drug resistance to drive outcome in serous ovarian cancer. American  Journal of  Cancer Research, 2015, 15; 5(6): 1862-77
  • Pandya, D., Marian, M., McHugh, M., Andreoli, M., Sieber, S., He, S., Dowell-Martino, C., Fiedler, P., Scambia, G, Ferlini, C. Herpes virus microRNA expression and significance in serous ovarian cancer. PLoS ONE, 2014, 9(12): e114750
  • Mariani, M., He, S., McHugh, M., Andreoli, M., Pandya, D, Sieber, S., Wu, Z., Fiedler, P., Shahabi, S., Ferlini, C.  Integrated multidimentional analysis is required for accurate prognostic biomarkers in colorectal cancer. PLoS ONE, 2014, 9(7): e101065.
  • Mariani, M., McHugh, M., Petrillo, M., Sieber, S., He, S., Wu, Z., Fiedler, P., Scambia, G., Shahabi, S., Ferlini, C. HGF/c-Met Axis Drives Cancer Aggressiveness in the Neo-adjuvant Setting of Ovarian Cancer.  Oncotarget, 2014, 5(13): 4232-44 
  • Paunovic, B., El-Fanek, H., Fiedler, P., Appel, C., Edwards, L. Colonic Schistosomiasis and Associated Cecal Neuroma. Connecticut Medicine, 2013, 77(6):339-42.