Postdoctoral Position Available

Andrew Fischer, M.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Pathology

Other Affiliation(s):
   Cell Biology

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 structure of the nuclear envelope in 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 tyrosine kinase—RET/PTC—that induces the nuclear envelope irregularity and chromatin dispersal diagnostic of papillary thyroid carcinoma.  We have determined the phosphotyrosine docking site on RET/PTC that mediates these changes.  Regarding the molecular basis of nuclear envelope irregularity, our studies suggest that the nuclear envelope composition is very similar between papillary thyroid carcinomas and normal thyroid.  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.  Recent exciting findings are that the chromatin dispersal may be associated with an alteration in histone H3 lysine 4 methylation.  Live cell imaging studies are underway to visualize the genesis of these changes in human thyroid cells’ native tissue microenvironment.  Such studies will allow us to test the contributions of chromatin and the cytoskeleton to the dynamic deformations of the nuclear envelope in this tumor. 

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.

Selected Publications:

Borrello MG, Alberti L, Fischer A, Degl’Innocenti D, Ferrario C, Gariboldi M, Marchesi F, Allavena P, Greco A, Collini P, Pilotti S, Cassinelli G, Bressan P, Fugazzola L, Mantovani A, Pierotti MA. Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene.  PNAS, 102(41):14825-14830, 2005.

Angeletti C, Harvey N, Khomitch V, Fischer A, Levenson R, and Rimm D.  Detection of malignancy in cytology specimens using spectral-spatial analysis.  Lab Invest, 85:1555-1564, 2005.

Jiang Z, Li C, Fischer A, Dresser K, Woda B. Using AMACR(P504S)/34bE12/p63 cocktail for the detection of small focal prostate carcinoma on needle biopsy specimens. Am J Clin Pathol 123(2):231-236, 2005.

Zink D, Fischer AH, Nickerson JA.  Nuclear structure in cancer cells.  Nature Reviews Cancer 4:677-687, 2004.

Rezk S, Brynes RK, Nelson V, Thein M, Patwardhan N, Fischer A, Khan A. b-Catenin expression in thyroid follicular lesions: Potential role in nuclear envelope changes in papillary carcinomas.  Endocrine Path 15 (4):329-38, 2004.

Hill DA, Chiosea S, Jamaluddin MS, Roy K, Fischer AH, Boyd D, Nickerson JA, and Imbalzano AN. Inducible changes in cell size and attachment area due to expression of a mutant SWI/SNF chromatin remodeling enzyme.  J Cell Sci 117(24):5847-54, 2004.

Fischer AH, Young K, DeLellis R:  Incorporating Pathologists’ criteria of malignancy into the evolutionary model for cancer development.  J Cellular Biochem 93(1):28-36, 2004.

Lin X, Fischer AH, Ryu KY, Cho JY,Kloos RT, Mazzaferri EL, Jhiang SM. Application of the Cre-LoxP system to enhance thyroid targeted expression of sodium iodide symporter.  J Clin Endocrin Metab. 89(5):2344-2350, 2004.

Fischer AH, Bardarov S, Jiang Z.  Molecular aspects of diagnostic nucleolar and nuclear envelope changes in prostate cancer.  J Cellular Biochem. 91:170-84, 2004

Fischer AH, Taysavang P, Jhiang SM. Nuclear envelope irregularity is induced by RET/PTC during interphase. Am J Pathol 163(3):1091-1099, 2003.

Zhu Z, Gandi 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 120(1):71-77, 2003.

Fischer AH, Taysavang P, Weber C, Wilson KL.  Nuclear envelope organization in papillary thyroid carcinoma. Histology and Histopathology 16(1): 1-14, 2001.

Academic Background:

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  

Office: Three Biotech
Phone: 508-793-6140
Fax: 508-793-6110
E-mail: Andrew.Fischer@umassmemorial.org
Keywords: Oncogenes/tumor suppressors, Cell Dynamics, Cancer Biology, Nuclear Architecture, Histopathology

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Postdoctoral Position Available http://www.umassmed.edu/pathology/fellowship/ One position is available in July 2009 for 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 (55,000 GYN, 8000 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.