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Elaine S. Jaffe, MD
Entry Id: TP-4

Eligibility Criteria
Qualified candidates must have completed an MD degree from an approved United States (US) or Canadian medical school or must hold an Educational Commission for Foreign Medical Graduates (ECFMG) certificate. Many candidates also have a PhD degree, and some have completed a general or subspecialty residency.

Overview
The Laboratory of Pathology (LP) offers a multifaceted training program for Residents in anatomic pathology at the National Institutes of Health (NIH) Clinical Center (CC). The Clinical Center is the site of intramural clinical research for the NIH (see http://www.nih.gov). Patients are enrolled in approximately 1,000 research protocols conducted by 15 institutes and centers. In addition, the staff of the LP receives more than 2,000 cases in consultation each year, resulting in a rich and diversified exposure to the practice of anatomic pathology.

The philosophy of the training program is to provide broad and in-depth exposure to the subject matter of anatomic pathology, with an emphasis on clinical correlation, relationships to disease mechanisms, and exposure to investigational opportunities. Each case under study is viewed in the context of 1) the individual patient's clinical course, 2) strong personal interactions with the clinicians caring for the patient, and 3) the general relevance to disease pathophysiology and investigational questions. Residents become fully grounded in the laboratory techniques, observational and descriptive analysis procedures, and communication skills required to gain the maximum information prior to rendering a diagnosis. Training occurs mostly within the Laboratory of Pathology and through our affiliations with the George Washington University Medical Center, and Children’s National Medical Center.

The research activities of the staff are diverse, incorporating the most modern techniques available in biomedical research and based upon a firm foundation of an intricate knowledge of the biology of the disease state. The laboratory also offers Accreditation Council for Graduate Medical Education (ACGME)-accredited subspecialty fellowships in cytopathology and hematopathology that integrate advanced diagnostic pathology with opportunities for laboratory research and instruction in sophisticated laboratory techniques.

Much of the strength of this residency-training program comes from the internationally recognized reputation of the Anatomic Pathology Staff. The staff is acclaimed in many areas of Anatomic Pathology and is committed to excellence in the teaching program. Because our clinical programs are integrated with the research activities of the NIH, our residents are exposed to information regarding the pathogenesis and pathophysiology of diseases that they are learning to diagnose on a regular basis. This insight into the basic disease mechanisms of pathology enhances their educational experience.

The training program has an abundance of formal courses, national meetings, and elective rotations at outstanding institutions across the country. The unique scientific environment of the NIH offers unmatched research opportunities, as well as a wealth of research conferences and lectures that supplement the clinical training. The superlative quality of our residents contributes significantly to the success of this program. LP consistently attracts top-rated candidates, many with both and MD and Ph.D. degree or additional post-graduate training or experience. Most of our past residents pursue careers in academic Pathology or biomedical research.

Structure of the Clinical Training Program
Clinical training in the Anatomic Pathology Program includes three years of rotations and subspecialty training. The program provides for diversified experience in postmortem, surgical pathology, cytopathology, hematopathology, molecular pathology and cytogenetics diagnosis. Separate one-month subspecialty rotations in forensic pathology, surgical pathology, and pediatric pathology offered at affiliated institutions broaden the training offered at the NIH. Integrated training in dermatopathology, neuropathology, pediatric pathology, flow cytometry, immunopathology, electron microscopy, informatics, management, and quality improvement are provided during all three years. Residents in the third year gain more authority in making diagnostic decisions and supervising other residents in both surgical and postmortem pathology. There are also further opportunities for clinical and research electives at this time.

The LP conducts a fully accredited AP3 program in Anatomic Pathology. An optional fourth year of training is fully funded at which time the residents may participate in electives or research. The sponsoring laboratory, LP or other, provides supplies and services for approved research rotations. During the fourth year, the resident's salary will be funded by LP, NCI for any combination of clinical and research rotations done within the Laboratory of Pathology, NCI. At the discretion of the Program Director, salary funding may be provided for research rotations in other NCI Laboratories and Branches. However, for laboratories outside of the NCI, the sponsoring laboratory/institute is expected to provide salary support for the fourth year resident.

Rounds, conferences, seminars, journal clubs, courses, and library resources
Residents attend regular departmental conferences and participate in Grand Round lectures (see http://calendar.nih.gov/app/MCalWelcome.aspx).

A schedule of lectures, seminars, journal clubs, and meetings is published each week and includes speakers of national and international note in all fields of biomedical science.

The National Library of Medicine is located on the grounds of the NIH and all its services are available. The Clinical Center has one of the most complete medical libraries in the country and the Laboratory of Pathology has a small departmental library. Scholarly activity includes active participation in regional or national professional and scientific societies. Many other educational opportunities are available at NIH.

Residents may receive some formal training through the NIH Foundation for Advanced Education in the Sciences (FAES). The ACGME accredits the NIH/FAES for sponsored continuing medical education for physicians.

After Hours and On-call Coverage
Residents are not required to be present at the institution during periods of on call. During the first two years of experience, the resident serves a total of seventeen weeks on call. Third-year Residents are relieved of call responsibilities but are available to advise and mentor junior residents. On-call schedules are fully in compliance with ACGME standards.

Resident Salaries and Benefits

• Residents receive appointments as Clinical Fellows (Civil Service). Clinical associates receive a starting salary of $51,782 per year for residents entering the program in July 2007. Additional compensation is provided for a post-baccalaureate degree (PhD) or for residents beyond the PGY1 year. A supplement of approximately $3400 is provided for on-call activities.
• Residents receive 2 weeks of paid vacation each year and 10 sick days per year. Other benefits include on-site childcare, moving allowance, and funding for scientific meetings and courses outside of the NIH. Resident shares costs of health insurance, and life insurance. Disability insurance is available at the resident’s expense. Residents may participate in federally sponsored retirement programs. Residents receive free parking or participate in the NIH Transhare Program to receive public transportation subsidies of up to $100 each month.
• Student Loan Repayment is available from $5,000 to $35,000 to qualified individuals accepted into the program.
• No living quarters are provided, but homes and apartments at all price levels are available in the immediate vicinity.
• The NIH is located in Bethesda, MD, a pleasant residential community just ten miles from the center of Washington, DC. All of the historic, social, and cultural advantages of the nation's capital are close at hand. There are five University Medical Centers in the area as well as the Armed Forces Institute of Pathology.

Clinical Cytogenetics

• Learn the indications for clinical cytogenetics testing.
• Become familiar with specimen requirements, and the various techniques used to process different tissues for cytogenetic analysis.
• Review the more common constitutional chromosomal abnormalities, and the mechanisms by which these abnormalities arise.
• Learn the more common, recurring chromosomal abnormalities found in hematologic malignancies and nonhematologic solid tumors, and the diagnostic and prognostic implications of these abnormalities.
• Participate in the interpretation and sign-out of current Clinical Cytogenetics Laboratory reports.

Cytopathology

• Learn to recognize cytomorphologic features of different cell types and range of normal morphology.
• Learn criteria of malignancy in various body sites and types of specimens.
• Gain experience in screening of cytology specimens to detect possibly rare abnormal cells amid a predominance of normal cells.
• Learn cytodiagnostic terminology for cervical/vaginal specimens.
• Learn limitations of cytopathologic diagnosis as compared to histopathologic diagnosis.
• Learn the appropriate use of ancillary diagnostic techniques such as immunocytochemistry and electron microscopy in the work-up of diagnostic problems encountered in cytopathology.
• Learn rapid triage of specimens in order to utilize patient material to best advantage in diagnostic work-up and avoid contamination of stains by highly cellular malignant fluids.
• Learn to recognize cell patterns that indicate a possible infectious process in order to consider options such as sending material to microbiology and/or obtaining special stains for organisms.
• Learn fundamentals of various specimen preparation techniques, including advantages and drawbacks of cytocentrifugation, membrane filtration, smears, and the new technology of monolayer ThinPreps.
• Appreciate the advantages and drawbacks of different staining methods such as wet fixed Papanicolaou versus air-dried modified Wright-Giemsa stains.
• Learn proper specimen collection techniques for various specimen types including cervical/vaginal smears and fine needle aspiration specimens.
• Learn fundamentals of quality assurance methods in pathology, particularly as applied to cytopathology.

Flow Cytometry

• Attain competency in interpreting flow cytometric histograms, dot plots, and contour plots.
• Understand the utility as well as the limits of the method and how the data generated integrates into the diagnostic interpretation.
• Acquire familiarity with criteria for diagnosis of malignant lymphoma using flow cytometry.
• Acquire familiarity with criteria for diagnosis of aneuploidy using DNA content analysis.
• Understand concept of determination of S phase fractions and variables important in this determination.
• Understand the need for quality control and know what currently is acceptable in this area.

Forensic Pathology

• Gain experience in the principles and practice of forensic pathology.
• Develop a systematic approach to the forensic autopsy, including evaluation of gross, microscopic, biochemical, and genetic evidence.
• Perform an autopsy safely, in an efficient, organized fashion.
• Interpret and correlate the postmortem pathologic findings with other clinical, laboratory, and evidentiary data.
• Learn to present autopsy findings to official personnel from the medical, legal, and investigative communities.

Hematopathology

• Prepare trainees to deliver state of the art diagnostic and consultative services in the field of hematopathology.
• Introduce trainees to research in hematopathology, and to inspire them to pursue a lifelong career of academic inquiry.
• Challenge trainees to think critically and in innovative ways about problems in hematopathology and to prepare them for a career of continued learning in pathology.
• Advance medical knowledge by striving for the highest standards of clinical care, scientific inquiry, and productivity.

Immunohistochemistry Laboratory

• Learn basic techniques of immunohistochemistry including methods of antigen retrieval.
• Learn how an immunohistochemistry lab is organized from specimen receipt to report generation.
• Learn to perform and interpret the common immunohistochemistry tests.
• Attend and present results of immunohistochemistry tests at a diagnostic conferences. These conferences emphasize the integration of the immunohistochemistry tests in the context of the whole case.
• Learn how to properly select and interpret appropriate controls.
• Develop the ability to be judicious in ordering practices.

In situ Hybridization

• Learn basic techniques of in situ hybridization.
• Learn how an in situ hybridization lab is organized from specimen receipt to report generation.
• Learn to perform and interpret the common in situ hybridization tests.
• Attend and present results of in situ hybridization tests at a diagnostic conferences. These conferences emphasize the integration of the in situ hybridization tests in the context of the whole case.
• Learn how to properly select and interpret appropriate controls.
• Develop the ability to be judicious in ordering practices.

Laboratory Management & Information Systems

• Develop an awareness of and responsiveness to the health care system, both at the National Institutes of Health, and in the broader national community.
• Develop the ability to effectively call on system resources to provide care that is of optimal value.

Molecular Pathology

• Learn basic techniques of nucleic acid handling, including proper storage of tissue samples and the extraction of intact materials from tissue samples.
• Learn electrophoresis methods for analysis of DNA and RNA, including agarose gel electrophoresis and acrylamide gel electrophoresis.
• Learn basic polymerase chain reaction (PCR) techniques to amplify targeted DNA from tissue samples. Learn how to select primers and proper controls.
• Learn basic Southern blot hybridization techniques.
• Learn how to label probes with nonisotopic methods.
• Learn basic methods of in situ hybridization of cytospins and tissue samples.
• Learn how a molecular diagnostics lab is organized from specimen receipt to report generation.
• Learn the proper set up to perform PCR laboratory so as to minimize the chances for contamination. Learn how to identify and handle contamination problems in the laboratory.
• Learn to perform and interpret the common molecular tests.
• Attend and present results of molecular diagnostics tests at a weekly molecular diagnostics conference. This conference emphasizes the integration of the molecular diagnostic test in the context of the whole case.

Neuropathology

• The overall objective is to learn those aspects of neuropathology particularly relevant to the practice of general anatomic pathology.
• Ensure proper neuropathologic examination; each case discussed with neuropathologist prior to autopsy vis-à-vis: a) special sampling, i.e., base of skull, sella turcica en bloc, orbital soft tissues, dorsal root ganglia, peripheral nerves, postmortem CSF by cisternal tap b) tissue handling: frozen tissue, fixation for EM.
• Be able to present the neurologic history and pertinent systemic clinical history at the brain cutting session with relevant areas of neuropathology discussion to follow.
• Be able to examine a brain for external evidence of disease or trauma.
• Be able to cut the brain with a purpose in mind.
• Be able to block in relevant sections.
• Be able to generate an order for relevant special stains needed for diagnosis.
• Learn basic neurohistology and generate a coherent, relevant, and concise neuropathologic autopsy report that integrates the history, gross, and microscopic findings.
• Learn how to handle neuropathologic surgical cases, including those submitted for frozen section.
• Evaluate the microscopic findings and order and interpret relevant special stains in neuropathologic biopsies.
• Learn how to generate a clearly written surgical pathology report containing that information specifically relevant to neurology and neurosurgery.

Pediatric Pathology

• Learn the principles and practice of pediatric pathology, and to acquire the skills necessary to function independently in the diagnosis of surgical and autopsy specimens in the pediatric age group.
• Recognize normal gross anatomical and histologic structures (including normal variants) as they pertain to surgical specimens.
• Process gross specimens appropriately as regards dissection, sampling, fixation, and special studies.
• Cut, stain, and interpret frozen section biopsies.
• Make diagnoses on surgical pathology specimens using gross, microscopic (H&E stains) and special studies.
• Write and dictate clear and concise surgical pathology reports.
• Organize the workload so that cases are processed, signed out and dictated in a timely manner.
• Communicate with clinicians in order to facilitate appropriate clinicopathologic correlations.
• Develop a systematic approach the evaluation of postmortem pathologic findings.
• Perform an autopsy safely, in an efficient, organized fashion.
• Interpret and correlate the postmortem pathologic findings with the clinical findings.
• Present autopsy findings to clinicians, both in written form (autopsy protocol in provisional and final states) as well as oral forms.

Postmortem Pathology

• Develop a systematic approach the evaluation of postmortem pathologic findings.
• Perform an autopsy safely, in an efficient, organized fashion.
• Interpret and correlate the postmortem pathologic findings with the clinical findings.
• Present autopsy findings to clinicians, both in written form (autopsy protocol in provisional and final states) as well as oral forms.
• Complete the autopsy report in a timely fashion; i.e., PA in 72 hours and FAD in 60 days.

Surgical Pathology

• The overall objective is to acquire the skills necessary to function independently in the diagnosis and interpretation of surgical pathology specimens.
• Recognize normal gross anatomical and histologic structures (including normal variants) as they pertain to surgical specimens.
• Process gross specimens appropriately as regards dissection, sampling, fixation, and special studies.
• Cut, stain, and interpret frozen section biopsies.
• Make diagnoses on surgical pathology specimens using gross, microscopic (H&E stains) and special studies.
• Write and dictate clear and concise surgical pathology reports.
• Organize the workload so that cases are processed, signed out and dictated in a timely manner.
• Communicate with clinicians in order to facilitate appropriate clinicopathologic correlations.

Ultrastructural Pathology

• Provide all residents with knowledge of the ultrastructure of pathologic conditions and with the understanding that the final diagnosis is the result of a combination of available methods.
• Familiarize residents with the ultrastructural features of pathologic conditions and to teach them how to use these features in combination with other available diagnostic tests and clinical information to reach a final diagnosis.

Clinical Proteomics
The Laboratory of Pathology Proteomics Core Lab provides 1) technical expertise in proteomic analyses for basic, translational and clinical research programs of collaborators primarily using current reverse phase protein microarray technology, in addition to other standard protein-based methods such as ELISA and western blotting; 2) training and technical assistance to interested users of the core lab for current protein microarray technology and automated microdissection; and 3) research and development advancing the science of high throughput protein microarray technology to support clinical proteomics, molecular diagnostics, and enhanced basic research programs.

Laser Capture Microdissection Core
Laser Capture Microdissection (LCM) was invented at the NIH. The LCM Core is directed by Dr. Michael Emmert-Buck, one of the inventors. The Core has several PixCell, Veritas, and AutoPix units. Residents may use the LCM core to aid in their research projects. Formal training and technical support is provided for users of the Core facility. Expression-based microdissection is currently under development, and an alpha test unit is in place at the NIH.

The residency-training program offers research-training opportunities virtually unmatched internationally. Each resident develops a research program with any of the world-renowned scientists in our Laboratory at the National Cancer Institute. Each resident plans a research project with a designated mentor and reviews the experimental plan with the Program Director. The residents are encouraged to choose exploratory projects, which lead to new discoveries and open new fields.

Residents are expected to serve as consultants and collaborators for clinical studies and case studies, which stem from findings made during routine diagnosis. During research rotations, each resident is provided with laboratory space, equipment, reagents and technical support. They show their research findings in weekly data clubs, and brainstorm ideas in weekly conferences and journal clubs. Research electives are concentrated in the later stages of the residency program. Residents receive two months of elective in the first year, three months of elective in the second year, and usually eight months of elective in the third year. These elective periods may be used for research rotations, or further clinical electives, depending on the needs and interests of the resident.

Each resident is provided with travel funds to attend one scientific conference per year. At that time the resident is responsible for a poster or platform presentation. Our residents have been highly successful at national meetings, and have been the recipients of numerous awards. Residents also compete for and obtain sponsorship for outside research electives.

Structure of the Research Training Program
The Laboratory of Pathology offers extensive training in experimental pathology. The research experience is rich and tailored to the background and interests of the resident. During the interview process the candidate meets with the clinical and basic science investigators in the department. After entering the program, the resident consults with the scientific staff and chooses a research project and advisor. At this time, laboratory bench space and access to all equipment and resources necessary to support the project are provided.

Some of the areas of investigation in which the trainees may participate include the following:

• Genetic and biochemical mechanisms of carcinogenesis
• Carbohydrate and protein receptors mediating cell adhesion and motility
• Extracellular matrix remodelling
• Oncogene transcriptional regulation
• Hematopathology, basic and applied molecular genetics research
• Pediatric tumor biology
• Applied surgical pathology studies in breast cancer, lung disease, drug resistance, gene product expression, and molecular markers of progression
• Technology development for biomedical research: laser capture microdissection, expression microdissection; specialized imaging techniques including spectral imaging and confocal microscopy.

Biochemical Pathology Section
Dr. David Roberts has discovered that thrombospondin-1 is an important physiologic inhibitor of vascular nitric oxide, signaling via cGMP in both endothelial and vascular smooth muscle cells; through this pathway, endogenous thrombospondin-1 limits angiogenesis, acutely regulates blood flow, and limits soft tissue survival of ischemia, and that nitric oxide-, thrombospondin-1-, and CD47 receptor-targeted drugs can improve survival of ischemic tissue. Dr. Roberts plays a leadership in three NCI Faculties: Vascular Biology Faculty (Chair of Steering Committee ), Molecular Targets Faculty (Steering Committee member ), Cancer Redox Biology Faculty (Steering Committee Co-chair ). He was instrumental in the formation of a new cancer redox biology initiative within the NCI.

Clinical Cytogenetics Section
Dr. Diane Arthur's research focuses on the clinical and biologic significance of chromosome abnormalities in human malignancies. Dr. Arthur directs a cytogenetics service that includes G-banding and interphase and metaphase fluorescence in-situ hybridization (FISH) of patient samples. Comparative genomic hybridization (CGH), and spectral karyotyping (SKYTm) are utilized for selected research protocols. Additionally, Dr. Arthur oversees the rotations in clinical cytogenetics for Residents and Fellows in LP, and has continued to organize and oversee the CAP accreditation activities of LP.

Cytopathology Section
Dr. Andrea Abati, Chief, Cytopathology Section, directs a state of the art cytopathology service that provides both diagnostic and clinical research support to a large number of NIH investigators and protocols. She utilizes novel cytopathologic methods to follow tumor responses to conventional chemotherapy, and cell-based and vaccine-based forms of cancer immunotherapy. Dr. Abati is a gifted educator, whose efforts have been rewarded by the outstanding performance of Residents and Fellows on certification examinations. She is the author of a textbook in the field, and currently serves as President of the Papanicolaou Society of Cytopathology. Dr. Armando Filie, Staff Clinician, is currently Program Director of the ACGME-accredited Cytopathology Fellowship, and was recognized by an NIH Director’s Award for his role in the cytopathology fellowship program.

Developmental Biology Unit
Dr. Susan Mackem is interested in the regulation of patterning and morphogenesis during development. Her lab is analyzing the function of several T-box and homeobox genes involved in both early inductive-patterning and in later growth phases of limb development. Emphasis is on deciphering developmental function in both chick and mouse embryos, including the use of conditional transgenic expression and knock-out approaches as well as biochemical analyses of mechanisms of gene regulation. Genomic approaches to identifying in vivo transcriptional targets, including microarray analysis and chromatin IP are also being developed in parallel. In addition, Dr. Mackem serves as an Attending Pathologist on the Autopsy Service.

Flow Cytometry Unit
Dr. Maryalice Stetler-Stevenson is recognized internationally as a leader in the field of clinical flow cytometry (FC). Among her many contributions, she demonstrated the clinical relevance and sensitivity of FC to detect low numbers of lymphoma cells in the CSF of patients with aggressive B-cell lymphomas (Blood, 105(2): 496-502, 2005). This observation has led to an international effort to apply FC for the monitoring of CSF disease in patients with lymphoma. Dr. Constance Yuan, an M.D., Ph.D. graduate of Thomas Jefferson Medical College, is board certified in anatomic and clinical pathology, and hematopathology. She plays a major role in the training of residents and fellows, in a program which features a case-based curriculum to master flow cytometric techniques.

Gene Regulation Section & Research Operations
Dr. David Levens is Director of Research Operations, and Chief, Gene Regulation Section. His discoveries provide a robust conceptual framework to explain the operation of the c-myc promoter. He dissected and reassembled a molecular servomechanism that programs the c-myc promoter; he showed that a dominant interfering splice variant of the FBP Interacting Repressor (FIR) contributes to c-myc overexpression and suppresses apoptosis in colon cancer; and demonstrated that topologically unconstrained DNA is functionally supercoiled during transcription. Dr. Levens is Chairman of the Integrative/Systems Biology Faculty, and developed a novel exchange pilot program with the U of MD in physics and applied mathematics. He is also Co-Chair of the Trans-NIH initiative in Systems Biology.

Hematopathology Section
Dr. Elaine Jaffe conducts a major program in diagnostic and experimental hematopathology. While the emphasis is on clinical protocols based at NCI, collaborations exist with physicians in other categorical institutes. Dr. Jaffe supervises an internationally recognized consultation service that receives over 1800 cases per year in consultation from the general medical community. The Hematopathology Section continues its active research program on the molecular and immunologic characterization of malignant lymphomas. Areas of emphasis include the interrelationship of Hodgkin's disease and the non-Hodgkin's lymphomas, T-cell lymphomas, and the role of Epstein-Barr virus in lymphoproliferative disorders. Dr. Jaffe is internationally recognized, and was recognized is being among the top 10 most highly cited physicians in the field of oncology for a 10 year period, 1988-1998. Dr. Stefania Pittaluga is the Program Director for a highly successful and competitive Hematopathology Fellowship program. She has received recognition from the NIH and the NCI for her exceptional abilities as a diagnostician and educator. In addition, she has developed an innovative program in imaging, employing both in situ hybridization and Quantum dots to visualize cells and molecules in the tissue environment.

Molecular Diagnostics/Immunohistochemistry Unit
Dr. Mark Raffeld, Director, Specialized Diagnostics Unit, provides molecular diagnostic and immunohistochemistry (IHC) services for pathology diagnosis and clinical protocol support. The molecular diagnostics service provides support for treatment protocols administered by more than 20 clinical investigators. The IHC service offers more than 300 antibodies for diagnostic testing, and works closely with basic and clinical investigators to implement testing using newly developed monoclonal and polyclonal antibodies. Dr. Raffeld is a valued and astute collaborator, and also has a successful research program investigating aberrant signalling pathways in mantle cell lymphoma (MCL) and anaplastic large cell lymphoma. His recent discovery of the involvement of the Akt pathway in a subset of MCL was highlighted by an editorial in Blood.

Pathogenetics Unit
Dr. Michael Emmert-Buck is Chief of the Pathogenetics Unit. An innovative and creative scientist, he invented a new operator-independent form of tissue dissection called expression microdissection (xMD). Two separate applications of xMD have been reduced-to-practice in the laboratory and prototype versions are being evaluated in pilot studies. He also has made major discoveries related to prostate cancer. He identified deregulated transcripts and proteins that are associated with human prostate cancer; and discovered a new epigenetic sub-microenvironment in prostate cancer that may be important in the pathogenesis of the disease. One of the original inventors of the laser capture microscope, he directs the LCM core for LP.

Pediatric Tumor Biology/Ultrastructural Pathology Section
Dr. Maria Tsokos directs the Ultrastructural Pathology service, and conducts a diagnostic and investigational program in Pediatric Tumor Biology. The electron microscopy unit has provided critical data for studies ranging from melanocyte development (J. Biol Chem 2007) to tumorigenesis of nerve root tissue (J Pathol 2006). Her research program focuses on the biology of pediatric tumors and the role of apoptotic pathways in tumor virulence and sensitivity to therapy.

Postmortem Pathology Section & Clinical Operations
Dr. David Kleiner works with the Liver Disease section of the NIDDK characterizing the hepatic pathologic changes in chronic viral hepatitis and steatohepatitis both on initial presentation and following treatment. Of particular interest are prognostic indicators of progression of fibrosis in these diseases. He also collaborates with the Transplantation Branch of the NIDDK studying the histopathologic effects of novel immunosuppressive regimens on the development of renal transplant rejection or other complications of transplantation. As Pathology Committee Chair for NASH Clinical Research Network, he led effort to define a scoring system for use in clinical trials (Hepatology 41: 1313-1321; 2005), and heads a group responsible for scoring of biopsies (800+ cases scored to date). He defined novel patterns of hepatic disease associated with chronic granulomatous disease, and identified new patterns of renal allograft rejection in recipients treated with T-cell depletional-induction regimens (Transplantation 80:1051-9; 2005).

The Postmortem Pathology Section serves as a diagnostic and education resource for the clinical staff as well as a source of research material for the study of diseases under protocol at the NIH Clinical Center. Other staff who rotate as Attendings on the Autopsy service include:

Dr. Carl C. Baker conducts research on human papillomaviruses and cervical cancer, including the molecular characterization of HPVs and their interaction with the host cell. Current interests include: 1) molecular characterization of cervical cancer progression, including microarray expression profiling; 2) alternative splicing of cellular and viral pre-mRNAs; 3) development of anti-HPV and anti-cervical cancer therapeutics using RNA trans-splicing.

Dr. Stephen M. Hewitt supervises the Tissue Array Research and Production Laboratory (TARP Lab). The TARP lab produces tissue arrays for both the extra-mural and intra-mural community. The intra-mural tissue arrays are constructed on a collaborative basis, and have included model systems for osteosarcoma, esophageal cancer, non-small cell lung cancer, lymphoma, mesothelioma, prostate cancer, and renal tumors as well as cell line arrays. Dr. Hewitt's interests include improving array technology, including automated arraying, data collection, quantitative methodologies for immunohistochemistry, and tissue-immunoblotting.

Dr. Alexander Vortmeyer is studying the molecular pathogenesis of CNS- and neural crest-derived neoplasms. He is a consultant neuropathologist to the LP, and conducts his primary research in NINDS.

Surgical Pathology Section
Dr. Maria Merino, Chief of the Surgical Pathology Section, has examined the histologic correlates of the hereditary renal cancer syndromes, and has studied the differences between hereditary and sporadically occurring renal carcinomas. She and her collaborators have identified genetic and proteomic markers in breast, prostate, thyroid and renal cell carcinomas. Dr. Martha Quezado provides expertise in a number of service areas as a specialist in GI pathology and a Board-Certified neuropathologist. She is the lead pathologist in the Clinical Inflammatory Bowel Disease Program. She characterized pathologically the inflammatory bowel disease (IBD) syndromes that occur in Hermansky-Pudlak syndrome, and common variable immunodeficiency disease. She has identified a subset of patients with glioblastoma multiforme with EGFR-amplification, who can benefit from anti-EGFR therapy. Dr. Chyi-Chia (Richard) Lee completed his pathology training at the University of Pennsylvania and Baylor University Medical School. His primary research and clinical area of expertise is dermatopathology.

Manuscripts published by program faculty members may be reviewed at http://ccr.cancer.gov/labs/lab.asp?labid=106.

Examples of Resident Publications

• Abou-Saif A, Lei J, McDonald TJ, Chakrabarti S, Waxman IF, Shojamanesh H, Schrump DS, Kleiner DE, Gibril F, Jensen RT. A new cause of Zollinger-Ellison syndrome: non-small cell lung cancer. Gastroenterology. 2001 Apr;120(5):1271-8.
• Berger AC, Alexander HR, Tang G, Wu PS, Hewitt SM, Turner E, Kruger E, Figg WD, Grove A, Kohn E, Stern D, Libutti SK (2000) Endothelial Monocyte Activating Polypeptide II Induces Endothelial Cell Apoptosis and May Inhibit Tumor Microvascular Research. 60:70-80.
• Carr K.M., Bittner M., Trent J.M. Gene-expression profiling in human cutaneous melanoma. Oncogene.  2003 May 19; 22(20):3076-80. Review. PMID: 12789283 [PubMed - indexed for MEDLINE]
• Carr K.M., Rosenblatt K., Petricoin E.F., Liotta L.A. Genomic and proteomic approaches for studying human cancer: prospects for true patient-tailored therapy. Hum Genomics.  2004 Jan;1(2):134-40. Review. PMID: 15601541 [PubMed - indexed for MEDLINE]
• Fountaine T.J., Wincovitch S.M., Geho D.H., Garfield S.H., Pittaluga S. Multispectral imaging of clinically relevant cellular targets in tonsil and lymphoid tissue using semiconductor quantum dots. Mod Pathol.  2006 Sep;19(9):1181-91. Epub 2006 Jun 16. PMID: 16778828 [PubMed - in process]
• Lei JY, Middleton LP, Guo XD, Duray PH, McWilliams G, Linehan WM, Merino MJ. Pigmented renal clear cell carcinoma with melanocytic differentiation. Hum Pathol. 2001 Feb;32(2):233-6.
• Lei JY, Wang Y, Jaffe ES, Turner ML, Raffeld M, Sorbara L, Morris J, Holland SM, Duray PH. Microcystic adnexal carcinoma associated with primary immunodeficiency, recurrent diffuse herpes simplex virus infection, and cutaneous T-cell lymphoma. Am J Dermatopathol. 2000 Dec;22(6):524-9.
• Mojica W.D., Rapkiewicz A.V., Liotta L.A., Espina V. Manual exfoliation of fresh tissue obviates the need for frozen sections for molecular profiling. Cancer.  2005 Dec 25; 105(6):483-91. PMID: 16015639 [PubMed - indexed for MEDLINE]
• Quezado M., Ronchetti R., Rapkiewicz A.V., Santi M., Blumenthal D.T., Rushing E.J. Chromogenic in situ hybridization accurately identifies EGFR amplification in small cell glioblastoma multiforme, a common subtype of primary GBM. Clin Neuropathol.  2005 Jul-Aug; 24(4):163-9. PMID: 16033132 [PubMed - indexed for MEDLINE]
• Rapkiewicz A.V., Espina V., Petricoin E.F. 3rd, Liotta L.A. Biomarkers of ovarian tumours. Eur J Cancer.  2004 Nov; 40(17):2604-12. Review. PMID: 15541961 [PubMed - indexed for MEDLINE]
• Rapkiewicz A.V., Hawk A., Noe A., Berman D.M. Surgical pathology in the era of the Civil War: the remarkable life and accomplishments of Joseph Janvier Woodward, M.D. Arch Pathol Lab Med.  2005 Oct; 129(10):1313-6. PMID: 16196522 [PubMed - indexed for MEDLINE]
• Robinson MR, Fine HF, Ross ML, Mont EK, Bryant-Greenwood PK, Hertle RW, Tisdale JF, Young NS, Zeichner SL, Van Waes C, Whitcup SM, Walsh TJ. Sino-orbital-cerebral aspergillosis in immunocompromised pediatric patients. Pediatr Infect Dis J. 2000 Dec;19(12):1197-203.
• Rosenblatt, K.P., Finkelstein, S.E., Cassarino, D.S., Fischette, M., Barnes, E., and Duray, P.H. (2001) Rapidly Progressive Melanoma (RPA). Abstr. USCAP Annual Mtg. 90: 412.
• Saif MW, Figg WD, Hewitt S, Brosky K, Reed E, and Dahut W. (2000) Malignant Ascites as Only Manifestation of Metastatic Prostate Cancer. Prostate Cancer and Prostate Disease 2, 290-293.
• Schiffmann R., Rapkiewicz A.V., Abu-Asab M., Ries M., Askari H., Tsokos M., Quezado M. Pathological findings in a patient with Fabry disease who died after 2.5 years of enzyme replacement. Virchows Arch.  2006 Mar;448(3):337-43. Epub 2005 Nov 29. PMID: 16315019 [PubMed - in process]
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The following is a list of recent graduates of the Laboratory of Pathology:

• Michael W. Beaty, MD: Wake Forest University School of Medicine
• Demetrious Braddock, MD, PhD: Yale University, School of Medicine
• Peter Bryant-Greenwood, MD: University of Hawaii
• Timothy Cote, MD, PhD: Centers for Disease Control
• Andrew Feldman, Mayo Clinic, Rochester, MN
• Michael Fritsch, MD, PhD: University of Wisconsin
• Thomas Giordano, M.D., Ph.D. University of Michigan
• Stephen Hewitt, MD, PhD: National Cancer Institute
• Alex E. Lash, MD: Memorial Sloan Kettering Cancer Center
• David Mauro, MD, PhD: Merck & Company
• Lavinia Middleton, MD: University of Texas M.D. Anderson Cancer Center
• Robert T. Pu, MD, PhD: University of Michigan School of Medicine
• Martha Quezado, MD: National Cancer Institute
• Julie Teruya-Feldstein, M.D., Memorial Sloan Kettering Cancer Institute
• Alexander O. Vortmeyer, MD, PhD: National Institute of Neurological Disorders and Stroke

Between 1955 and 2001, 143 residents have graduated from the program. Professional appointment after completion of the residency program are approximately 41% non-government academic pathology, 40% government position academic pathology, 18% community service pathology, and < 1% industry. Over 12 graduates currently serve as departmental chairpersons or academic deans.

The Anatomic Pathology Program at NIH is fully accredited by the Accreditation Council for Graduate Medical Education. Upon completion of the four year program, residents are fully eligible to sit for boards in anatomic pathology. Qualified candidates must have completed at least an MD degree. Many candidates also have a PhD degree, and some have completed a general or subspecialty residency. There are three to four positions available per year, and candidates should apply from nine months to a year in advance. Residents usually stay in the program for three to four years.

Electronic Application
We do not participate in the National Resident Matching Program (NRMP) but do accept applications through ERAS. You may also submit the following information to Ms. Susan Hostler, Admissions Coordinator:

• Completed application form. Please contact Ms. Susan Hostler (hostlers@mail.nih.gov or 301-402-3990) for an application form.
• Letters of recommendation should be solicited from the four individuals listed as references on the application form and directed to Dr. Elaine S. Jaffe. One of the letters may be a Dean's letter, but a Dean's letter is not required for processing of the application.
• Detailed Curriculum Vitae and Bibliography
• Transcripts of medical school training
• A narrative letter describing your reasons for specializing in pathology, any previous experience in teaching or research, and your ultimate career goals. Please discuss any special interests you have within the field of anatomic pathology
• Foreign medical graduates: Please include a copy of your E.C.F.M.G. certificate and English translation of your Medical School Diploma if this was issued in a language other than English or Latin. Please note that applications with pending E.C.F.M.G. scores will not be considered until after the E.C.F.M.G. certificate has been issued.
  

Please mail the above to:
Ms. Susan Hostler
Laboratory of Pathology, CCR, NCI
10 Center Drive, Room 2A33 MSC 1500
National Institutes of Health
Bethesda, MD 20892

Only three positions are open to new applicants each year. Applications should be submitted by November 1st for appointments beginning the following July 1st. After review of completed applications, qualified candidates will be invited to meet our staff and residents.

The NIH is dedicated to building a diverse community in its training and employment programs.