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    Andrew H Fischer MD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentPathology
    AddressUniversity of Massachusetts Medical School
    One Innovation Drive, Biotech Three
    Worcester MA 01605
    Phone508-856-6435
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentCell and Developmental Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentClinical Population Health Research

        Overview 
        Narrative

        Academic Background:

        BS (Cell Biology), 1979, Cornell University, Ithaca, NY

        MD, 1984, Brown University, Providence, Rhode Island

        Resident, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 1984-1988

        Cytopathology Fellow with Prabodh Gupta, Hospital of the University of Pennsylvania, Philadelphia, PA 1988-1989

        Cytopathology Fellowship Available-

        One position is availablefor an ACGME-accredited one-year Cytopathology Fellowship. The Fellowship is unique in integrating Cell Biology concepts related to Cytopathology, and offering basic research opportunities directly related to Cell Biology and Cytopathology into the year. Candidates must be AP or AP/CP eligible, and preference will be given to candidates interested in participating in ongoing research relating to the molecular basis of diagnostic morphologic cellular changes in cancer. The full curriculum includes a strong foundation in classical morphologic diagnosis (75,000 GYN, 10,000 non-GYN per year), FNA performance and interpretation (total 2000 FNA's per year), integration of Molecular Pathology and flow cytometry, cytopreparatory methods, and laboratory management. Stipend is determined by years of post-graduate experience. Clickherefor more information.

        Academic Interests:

        Cytology is the field that uses the smallest possible biopsy for diagnosis, by identifying structuralchanges in cells and small tissue fragments. My basic research interest has been to try to define diagnostic structural changes in molecular terms (see Basic Science Research Interest below).Dr. Fischer's picture

        My clinical interest is fine needle aspiration (FNA) biopsy. FNAs are minimally invasive, safe, rapid, and relatively painless means of definitive diagnosis. Having performed over 2,500 FNAs in my career so far, a UMASS FNA Clinic has been started whereby a Cytopathologist performs and immediately interprets the FNA. It is more efficient for cytopathologists to perform the biopsy that they diagnose.

        I have also been interested in developing technical solutions to the problem of acquiring and processing microsized pieces of tissue for diagnosis. Through grants from the Department of Pathology and the University of Massachusetts, I invented the CellientTM Automated Cell Block System (US Patents 6,913,921 and 7,541,161, with three other pending patents). Licensed to Hologic Corporation in Marlborough, MA, CellientTM automatically recovers small tissue fragments from a specimen container and rapidly delivers them to an indexable plane in paraffin for histologic sectioning, in under one hour. CellientTM allows fine needle (22-25 guage) biopsies to be examined in essentially the same manner as much larger core biopsies. Several other invention disclosures to the Office of Technology Management at UMASS have been made relating to improving microbiopsy needles, assessing the quality of a microbiopsy sample at the bedside, and developing automated means of processing and embedding histology samples.

        As criteria become defined at a molecular level, and techniques for procuring and handling micro-sized biopsies are developed, most cancers can be diagnosed with minimally invasive, rapid, and safe cytologic techniques.

        Basic Science Research Interests:

        In spite of years of progress in cancer research, the diagnosis of cancer still generally requires a pathologist to examine a biopsy by light microscopy. Cytopathologists are experts at recognizing changes in cell structure that are diagnostic of various cancers. Surprisingly, cancer researchers still know very little about how or why cancer cells are structured differently from normal cells.My long term goal is to learn the biochemical basis and functional significance of diagnostic changes in the nuclear structure of cancer cells. My lab has developed the idea that cellular-level structural changes diagnostic of cancer are directly caused by the particular cancer genes active in that cancer. We have linked 8 different cancer genes to large scale cellular structural changes, involving chromatin and the nuclear envelope, characteristic of different types of cancers. We think that the structural changes oncogenes induce during their activation provide an essential insight into the functional changes that occur during carcinogenesis.

        Nuclear envelope irregularity and changes in large-scale chromatin organization are important diagnostic alterations in many forms of cancer. We are focused on a pair of tyrosine kinases—RET/PTC and TRK/PTC—that induce the nuclear envelope irregularity and chromatin dispersal diagnostic of papillary thyroid carcinoma. We have determined the phosphotyrosine docking site on these kinases that mediates these changes. We showed that the nuclear lamina composition is very similar between papillary thyroid carcinomas and normal thyroid, and histone composition at a global level is not apparently altered for H3K4m, H3K9m, H3K9/14Ac, and H3K27m. Using micro-injection of RET/PTC into normal thyroid cells in culture, we showed that nuclear envelope irregularity develops during interphase, without an intervening post-mitotic nuclear envelope reassembly, because the nuclear envelope is distorted actively during interphase by forces exerted on it from the cytoskeleton and/or chromatin. More recently, we confirmed that there are active interphase deflections of the nuclear lamina in prostate cancer, and we found that depolymerization of actin or microtubules does not inhibit these dynamics. My lab is interested in developing live cell imaging techniques that can be applied to organ cultures to study the dynamics of nuclear lamina alterations in cancer cells and dependence of lamina dynamics on cell cycle phase or active transcription.

        The paradigm that cancer genes are linked very directly to diagnostic cell structural changes should lead to improved diagnosis of cancer, insight into novel cell physiologies involving chromatin and the nuclear envelope, and a basis for a large-scale screen for novel anticancer drugs.Live cell imaging techniques seem likely to expose new sets of dynamic structural changes with a diagnostic utility surpassing that of classical static imaging.



        Bibliographic 
        selected publications
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        1. Hatch EM, Fischer AH, Deerinck TJ, Hetzer MW. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell. 2013 Jul 3; 154(1):47-60.
          View in: PubMed
        2. Fischer AH, Benedict CC, Amrikachi M. Five top stories in cytopathology. Arch Pathol Lab Med. 2013 Jul; 137(7):894-906.
          View in: PubMed
        3. Wernicke AG, Greenwood EA, Coplowitz S, Parashar B, Kulidzhanov F, Christos PJ, Fischer A, Nori D, Chao KS. Tissue Compliance Meter is a More Reproducible Method of Measuring Radiation-Induced Fibrosis than Late Effects of Normal Tissue-Subjective Objective Management Analytical in Patients Treated with Intracavitary Brachytherapy Accelerated Partial Breast Irradiation: Results of a Prospective Trial. Breast J. 2013 May; 19(3):250-8.
          View in: PubMed
        4. Moriarty AT, Bentz JS, Winkler B, Fischer AH, Laucirica R, Souers RJ, Thomas N, Zhao C. The College of American Pathologists' first 3 years' experience with high-risk human papillomavirus proficiency testing for cytology and other laboratories. Arch Pathol Lab Med. 2013 May; 137(5):606-9.
          View in: PubMed
        5. Fischer AH, Clayton AC, Bentz JS, Wasserman PG, Henry MR, Souers RJ, Moriarty AT. Performance differences between conventional smears and liquid-based preparations of thyroid fine-needle aspiration samples: analysis of 47,076 responses in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology. Arch Pathol Lab Med. 2013 Jan; 137(1):26-31.
          View in: PubMed
        6. Chen Y, Liang CP, Liu Y, Fischer AH, Parwani AV, Pantanowitz L. Review of advanced imaging techniques. J Pathol Inform. 2012; 3:22.
          View in: PubMed
        7. Jean-Gilles J, Fischer AH, Luu MH, Owens CL. Clinical and pathologic features and clinical impact of false negative thyroid fine-needle aspirations. Cancer Cytopathol. 2012 Oct 25; 120(5):326-33.
          View in: PubMed
        8. Luu MH, Fischer AH, Stockl TJ, Pisharodi L, Owens CL. Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis. Acta Cytol. 2011; 55(6):526-30.
          View in: PubMed
        9. Paull PE, Hyatt BJ, Wassef W, Fischer AH. Confocal laser endomicroscopy: a primer for pathologists. Arch Pathol Lab Med. 2011 Oct; 135(10):1343-8.
          View in: PubMed
        10. Stuckey A, Fischer A, Miller DH, Hillenmeyer S, Kim KK, Ritz A, Singh RK, Raphael BJ, Brard L, Brodsky AS. Integrated genomics of ovarian xenograft tumor progression and chemotherapy response. BMC Cancer. 2011; 11:308.
          View in: PubMed
        11. Fischer AH, Cibas ES, Howell LP, Kurian EM, Laucirica R, Moriarty AT, Renshaw AA, Zakowski MF, Young NA. Role of cytology in the management of non-small-cell lung cancer. J Clin Oncol. 2011 Aug 20; 29(24):3331-2.
          View in: PubMed
        12. Nucera C, Nehs MA, Nagarkatti SS, Sadow PM, Mekel M, Fischer AH, Lin PS, Bollag GE, Lawler J, Hodin RA, Parangi S. Targeting BRAFV600E with PLX4720 Displays Potent Antimigratory and Anti-invasive Activity in Preclinical Models of Human Thyroid Cancer. Oncologist. 2011; 16(3):296-309.
          View in: PubMed
        13. Schmolze DB, Standley C, Fogarty KE, Fischer AH. Advances in microscopy techniques. Arch Pathol Lab Med. 2011 Feb; 135(2):255-63.
          View in: PubMed
        14. Luu MH, Fischer AH, Pisharodi L, Owens CL. Improved preoperative definitive diagnosis of papillary thyroid carcinoma in FNAs prepared with both ThinPrep and conventional smears compared with FNAs prepared with ThinPrep alone. Cancer Cytopathol. 2011 Feb 25; 119(1):68-73.
          View in: PubMed
        15. Fischer AH, Zhao C, Li QK, Gustafson KS, Eltoum IE, Tambouret R, Benstein B, Savaloja LC, Kulesza P. The cytologic criteria of malignancy. J Cell Biochem. 2010 Jul 1; 110(4):795-811.
          View in: PubMed
        16. Wernicke AG, Parashar B, Kulidzhanov F, Riley L, Christos PJ, Fischer A, Nori D, Chao KS. Prospective study validating inter- and intraobserver variability of tissue compliance meter in breast tissue of healthy volunteers: potential implications for patients with radiation-induced fibrosis of the breast. Int J Radiat Oncol Biol Phys. 2011 May 1; 80(1):39-46.
          View in: PubMed
        17. Wernicke AG, Rosenblatt R, Rasca M, Parhar P, Christos PJ, Fischer A, Parashar B, Nori D. Quantitative assessment of radiation-induced fibrosis of the breast with tissue compliance meter, palpation, and radiological imaging: preliminary results. Breast J. 2009 Nov-Dec; 15(6):583-92.
          View in: PubMed
        18. Fischer AH. Circulating tumor cells: seeing is believing. Arch Pathol Lab Med. 2009 Sep; 133(9):1367-9.
          View in: PubMed
        19. Jaffar R, Mohanty SK, Khan A, Fischer AH. Hemosiderin laden macrophages and hemosiderin within follicular cells distinguish benign follicular lesions from follicular neoplasms. Cytojournal. 2009; 6:3.
          View in: PubMed
        20. Slosar M, Vohra P, Prasad M, Fischer A, Quinlan R, Khan A. Insulin-like growth factor mRNA binding protein 3 (IMP3) is differentially expressed in benign and malignant follicular patterned thyroid tumors. Endocr Pathol. 2009; 20(3):149-57.
          View in: PubMed
        21. Fischer AH, Jacobson KA, Rose J, Zeller R. Cryosectioning tissues. CSH Protoc. 2008; 2008:pdb.prot4991.
          View in: PubMed
        22. Fischer AH, Jacobson KA, Rose J, Zeller R. Paraffin embedding tissue samples for sectioning. CSH Protoc. 2008; 2008:pdb.prot4989.
          View in: PubMed
        23. Fischer AH, Jacobson KA, Rose J, Zeller R. Fixation and permeabilization of cells and tissues. CSH Protoc. 2008; 2008:pdb.top36.
          View in: PubMed
        24. Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc. 2008; 2008:pdb.prot4986.
          View in: PubMed
        25. Fischer AH, Jacobson KA, Rose J, Zeller R. Preparation of slides and coverslips for microscopy. CSH Protoc. 2008; 2008:pdb.prot4988.
          View in: PubMed
        26. Fischer AH, Jacobson KA, Rose J, Zeller R. Decalcifying tissues for paraffin embedding. CSH Protoc. 2008; 2008:pdb.prot4990.
          View in: PubMed
        27. Fischer AH, Jacobson KA, Rose J, Zeller R. Cutting sections of paraffin-embedded tissues. CSH Protoc. 2008; 2008:pdb.prot4987.
          View in: PubMed
        28. Fischer AH, Jacobson KA, Rose J, Zeller R. Media for mounting fixed cells on microscope slides. CSH Protoc. 2008; 2008:pdb.ip52.
          View in: PubMed
        29. Yantiss RK, Cosar E, Fischer AH. Use of IMP3 in identification of carcinoma in fine needle aspiration biopsies of pancreas. Acta Cytol. 2008 Mar-Apr; 52(2):133-8.
          View in: PubMed
        30. Fischer AH, Jacobson KA, Rose J, Zeller R. Mounting live cells attached to coverslips for microscopy. CSH Protoc. 2008; 2008:pdb.prot4927.
          View in: PubMed
        31. Li C, Zota V, Woda BA, Rock KL, Fraire AE, Jiang Z, Lu D, Xu B, Dresser K, Lutman CV, Fischer AH. Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations. Mod Pathol. 2007 Dec; 20(12):1263-8.
          View in: PubMed
        32. Istvanic S, Fischer AH, Banner BF, Eaton DM, Larkin AC, Khan A. Cell blocks of breast FNAs frequently allow diagnosis of invasion or histological classification of proliferative changes. Diagn Cytopathol. 2007 May; 35(5):263-9.
          View in: PubMed
        33. Underwood JM, Imbalzano KM, Weaver VM, Fischer AH, Imbalzano AN, Nickerson JA. The ultrastructure of MCF-10A acini. J Cell Physiol. 2006 Jul; 208(1):141-8.
          View in: PubMed
        34. Angeletti C, Harvey NR, Khomitch V, Fischer AH, Levenson RM, Rimm DL. Detection of malignancy in cytology specimens using spectral-spatial analysis. Lab Invest. 2005 Dec; 85(12):1555-64.
          View in: PubMed
        35. Jiang Z, Li C, Fischer A, Dresser K, Woda BA. Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens. Am J Clin Pathol. 2005 Feb; 123(2):231-6.
          View in: PubMed
        36. Hill DA, Chiosea S, Jamaluddin S, Roy K, Fischer AH, Boyd DD, Nickerson JA, Imbalzano AN. Inducible changes in cell size and attachment area due to expression of a mutant SWI/SNF chromatin remodeling enzyme. J Cell Sci. 2004 Nov 15; 117(Pt 24):5847-54.
          View in: PubMed
        37. Zink D, Fischer AH, Nickerson JA. Nuclear structure in cancer cells. Nat Rev Cancer. 2004 Sep; 4(9):677-87.
          View in: PubMed
        38. Fischer AH, Young KA, DeLellis RA. Incorporating pathologists' criteria of malignancy into the evolutionary model for cancer development. J Cell Biochem. 2004 Sep 1; 93(1):28-36.
          View in: PubMed
        39. Lin X, Fischer AH, Ryu KY, Cho JY, Sferra TJ, Kloos RT, Mazzaferri EL, Jhiang SM. Application of the Cre/loxP system to enhance thyroid-targeted expression of sodium/iodide symporter. J Clin Endocrinol Metab. 2004 May; 89(5):2344-50.
          View in: PubMed
        40. Fischer AH, Bardarov S, Jiang Z. Molecular aspects of diagnostic nucleolar and nuclear envelope changes in prostate cancer. J Cell Biochem. 2004 Jan 1; 91(1):170-84.
          View in: PubMed
        41. Fischer AH, Taysavang P, Jhiang SM. Nuclear envelope irregularity is induced by RET/PTC during interphase. Am J Pathol. 2003 Sep; 163(3):1091-100.
          View in: PubMed
        42. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am J Clin Pathol. 2003 Jul; 120(1):71-7.
          View in: PubMed
        43. Fischer AH. The evolution of tumor biology: seeking a balance between gene expression profiling and morphology studies. J Mol Diagn. 2002 Feb; 4(1):65.
          View in: PubMed
        44. Kaufman HL, Fischer AH, Carroll M, Becker JM. Colonic ulceration associated with nonsteroidal anti-inflammatory drugs. Report of three cases. Dis Colon Rectum. 1996 Jun; 39(6):705-10.
          View in: PubMed
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