NEW YORK UNIVERSITY SCHOOL OF MEDICINE GRADUATE EDUCATION IN THE DEPARTMENT OF PATHOLOGY

PATHOBIOLOGY & TRANSLATIONAL MEDICINE

TRAINING PROGRAM

The image is part of the following manuscript: In Vivo mapping of notch pathway activity in normal and stress hematopoiesis.

<http://www.ncbi.nlm.nih.gov/pubmed/23791481> Oh P, Lobry C, Gao J, Tikhonova A, Loizou E, Manent J, van Handel B,

Ibrahim S, Greve J, Mikkola H, Artavanis-Tsakonas S, Aifantis I. Cell Stem Cell. 2013 Aug 1;13(2):190-204. In this study Dr.

Aifantis's group employed novel genetic tools to map the activity of Notch signaling pathway in vivo. The following image is

Immuno fluorescent staining of the spleen taken from Hes1GFP mouse, in which cells that are actively signal though Notch

receptor(s)are labeled with green fluorescent protein (GFP). Spleen's architecture is classically defined by red and

white pulp. Here, the red and purple colors mark hematopoetic populations that reside within the red-pulp portion of the

spleen. This image captures localization of Notch-signaling cells (green) within the landscape of the organ.

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N EW Y ORK UNIVERSITY SCHOOL OF MEDICINE GRADUATE EDUCATION IN THE DEPARTMENT OF PATHOLOGY

Contents

! Overview and welcome Letter from the Program and Course

Directors ! List of Pathobiology Faculty

! Curriculum Overview

! Courses Sponsored by the Pathobiology Program

- Introduction to Tissues and Organ Systems - Advanced Tissues and Organ Systems - Molecular Pathology in Omics Era

! Seminar in Pathology (Work in Progress -- WIP) – 2014-2015

Series

! Patholobiology & Translational Medicine Retreat & Research Day - 2015

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Pathobiology & Translational Medicine Program Overview – Welcome Letter from the Program and Course Directors

Dear Sackler Students, The recognition that the fruits of basic biomedical research are now ripe for translation into clinical practice has created a great need for translational scientists - individuals who can both interface with clinicians to strengthen clinical research, as well as capitalize upon clinical problems to inform more basic laboratory bench research endeavors. Traditionally, the training of such translational scientists has relied upon the Medical Scientist Training Program (MSTP) and the granting of dual MD/PhD degrees. However, this approach does not leverage the talents of those obtaining PhD degrees who could make substantial contributions to translational medicine if equipped with the appropriate tools and if sufficiently exposed to clinical medicine early in their training. Our Pathobiology & Translational Medicine Training Program provides such training. Our program is unique at the New York University School of Medicine (NYUSoM) within the Sackler Institute of Graduate Biomedical Sciences and prepares the next generation of biomedical scientists to lead the discovery of innovative diagnostic and therapeutic strategies in modern medicine. The training program accomplishes this through rigorous training in hypothesis-driven basic science research embedded within a rich curriculum of clinical medicine, all housed within a world-class medical center. Our students experience didactic learning and perform research within six scientifically-diverse “cluster” areas: I) cardiopulmonary medicine and hematology; II) gastrointestinal, genitourinary and

integument; III) autoimmunity, infection and inflammation; IV) translational oncology and stem cell biology; V) endocrine, metabolism and diabetes; and VI) neurobiology and neurodegeneration. The Centers for Disease Control and Prevention reported that the leading causes of death in the US in 2010 were heart disease, cancer, respiratory disease, stroke, Alzheimer’s disease, diabetes, kidney diseases and influenza/pneumonia (http://www.cdc.gov). All of these subject areas are very well-represented within our six cluster areas, underscoring the broad impact of our training program to many different important disease entities. Our program promotes this understanding through:

1) a pathobiology and translational medicine curriculum carefully designed to present an integrated view of pathogenesis at the molecular, cellular, tissue, organ system, and organismal levels; 2) co-mentorship of dissertation projects by a relevant clinician as well as the student’s principal advisor; and 3) targeted clinical correlation experiences guided by practicing pathologists and research-oriented physicians.

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Together with exceptionally-strong biomedical research within our six cluster areas, these clinical rotations and co-mentoring train the students in a collaborative, team-oriented research setting that helps prepare them for what we believe will become a dominant paradigm in biological research over the next decade.

The materials in this folder provide information about our curriculum, specifics about our courses, and a list of our participating faculty.

We are excited to be bringing you this program, designed to take full advantage of the fact that our Graduate School is located in the heart of a great academic medical center. Please do not hesitate to contact any one of us if you desire any additional information, or visit our websites at: http://pathology.med.nyu.edu/education.

Sincerely,

Program Co-Directors: Ann Marie Schmidt, M.D. AnnMarie.Schmidt@nyumc.org

Adrian Erlebacher, M.D.-Ph.D. Adrian.Erlebacher@nyumc.org

Iannis Aifantis, Ph.D. Iannis.aifantis@nyumc.org

Graduate Advisors: Jorge Ghiso, Ph.D Jorge.Ghiso@nyumc.org

Cindy Loomis, M.D.-Ph.D. Cynthia.Loomis@nyumc.org

Senior Faculty & Course-Directors: Stefan Feske, M.D. Stefan.Feske@nyumc.org

Eva Hernando, Ph.D. Eva.Hernando@nyumc.org

David Zagzag, M.D. David.Zagzag@nyumc.org

Clinical Curriculum Team: Antonio Neto Galvao, M.D. Antonio.GalvaoNeto@nyumc.org

Matija Snuderl, M.D. Matija.Snuderl@nyumc.org

Jonathan Melamed, M.D. Jonathan.Melamed@nyumc.org

John Munger, M.D. John.Munger@nyumc.org

Pamela Rosenthal, M.D. Pamela.Rosenthal@nyumc.org

Amy Rapkiewicz, M.D. Amy.Rapkiewicz@nyumc.org

Pathobiology & Translational Medicine Training Faculty

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Aifantis, Iannis, PhD Pathology, Chair (HHMI) Hematopoietic stem cell differentiation, leukemia,

Ubiquitination, epigenetic regulation of stem cell activity

Barcellos-Hoff, Mary Helen, PhD

Radiation Oncology (Cell Biology)

Multicellular processes during progression from normal to neoplastic condition in breast cancer and ionizing radiation

Berger, Jeffrey Medicine (Cardiology) Platelet-vascular interactions and cardiovascular disease

Blaser, Martin, MD Internal Medicine (Microbiology)

Biology of H. pylori colonization and the nature of the interactions that lead to disease, gut microbiome and host interactions

Buyon, Jill, MD Medicine Maternal Anti-SSA/Ro-SSB/La Antibodies and Pathogenesis of Congenital Heart Block

Cadwell, Ken, PhD Microbiology (Skirball) Host-pathogen interactions in inflammatory disease

Carr, Kenneth, PhD Biochemistry and Molecular Pharmacology (Psychiatry)

Neurobiology of Ingestive Behavior and Drug Addiction

Carroll, William, MD Pediatrics (Oncology, Cancer Institute, Pathology)

Treatment of childhood cancer, especially leukemias and the common solid tumor neuroblastoma

Coetzee, William, D.Sc Biochemistry and Molecular Pharmacology (Pediatrics)

Electrophysiology and Molecular Biology of Cardiovascular Membrane Ion Transport Proteins

Cowin, Pamela, PhD Dermatology (Cell Biology) Cell Adhesion and Wnt Signaling

Cronstein, Bruce, MD Biochemistry and Molecular Pharmacology (Medicine-Pharmacology)

Adenosine-mediated regulation of inflammation, wound healing, fibrosis and bone resorption and the pharmacology of adenosine receptors

David, Gregory, PhD Pharmacology Chromatin modifications in development and oncogenesis

Erlebacher, Adrian, MD, PhD

Pathology Immunobiology of pregnancy, peripheral immune tolerance, immune regulation in cancer

Ernst, Joel MD Medicine (Infectious Disease) Tuberculosis and host-pathogen interactions

Feske, Stefan, MD Pathology Calcium channels in T cell activation, immunity and leukemia

Fine, Howard Medicine (Heme-Oncology) Mechanisms of glioblastoma

Fisher, Edwards, PhD, MPH, MD

Medicine-Cardiology (Pediatrics, Cell Biology)

The cell biology of hepatic lipid and lipoprotein metabolism and he molecular biology of vascular diseases

Fishman, Glenn, MD Medicine-Cardiology (Biochemistry and Molecular Pharmacology)

Cardiovascular genetics; cardiovascular development; cardiac electrophysiology and arrhythmias

Frey, Alan, PhD Cell Biology CD8+ T Cell immune response to cancer

Garabedian, Michael, PhD

Microbiology (Urology) Mechanism of steroid hormone receptor action; androgen receptor in prostate cancer

Ghiso, Jorge, PhD Pathology (Psychiatry) Amyloid proteins and fibrillogenesis, molecular mechanisms of neurodegeneration

Goldberg, Ira MD Medicine Diabetic complications, lipotoxicity, lipid metabolism

Hernando, Eva, PhD Pathology Cell-of-origin, 'cancer stem cells', mech. of tumor initiation/progression

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Hubbard, Jane, PhD Pathology (Skirball Institute) Control of cell proliferation using the C. elegans germ line as a model system

Keefe, David, MD Obstetrics and Gynecology (Cell Biology)

Reproductive aging, Oocyte dysfunction, telomeres, meiosis, stem cells

Koralov, Sergei, PhD Pathology The role of RNAi in B cell development and function; the role of short non-coding RNAs in epigenetic control of Ig loci

Laal, Suman, PhD Pathology (Microbiology) Immunol. and Mol. Biol. of Mycobacteria, Opportun. infection in HIV disease

Lafaille, Juan, PhD Pathology Pathogenesis of autoimmune and allergic diseases, regulatory T cells

Lee, Peng, PhD Pathology (Urology) Androgen receptor function, cofactors and target genes in prostate and breast cancer

Levy, David, PhD Pathology (Microbiology) Cytokine signal transduction and gene expression in growth control and cancer

Littman, Dan PhD Molecular Pathogenesis, Pathology, Microbiology, Skirball Institute

Molecular events underlying T-lymphocyte differentiation and activation

Logan, Susan, PhD Urology (Pharmacology) Cell growth regulation through the androgen receptor Loke, P’ng PhD Microbiology Helminth infections and the role of immune

responses Mathews, Paul, PhD Psychiatry Understanding the role of the endosomal-lysosomal

system in neurodegeneration Meruelo, Daniel, PhD Pathology Gene therapy, cancer, Alzheimer’s disease

Moore, Kathryn, PhD Medicine (Cell Biology) The role of the innate immune system in sterile inflammatory conditions and host defense, and

Morley, Greg, PhD Medicine (Physiology, Neuroscience)

The fundamental mechanisms of impulse initiation and conduction and the role they play in triggering and maintaining cardiac arrhythmias.

Munger, John, MD Medicine (Cell Biology) How integrins activate latent TGFβ1 and TGFβ3 during development and in disease

Nyambi, Phillipe, PhD Pathology Antigenic evol. of HIV-1 subtype B/non B viruses, HIV-1 Immuno-, Serotypes

Osman, Iman, MD Medicine (Dermatology, Urology)

Melanoma, Interdisciplinary Melanoma Cooperative Program (IMCG) Racial Dispartity in Genitourinary Oncology

Pagano, Michele, MD Oncology/ Pathology (HHMI, Cancer Institute)

Ubiquitin system, cell division cycle checkpoints, cancer

Pei, Zhiheng, MD, PhD Pathology Bacteria microbiome inflammation esophagus tonsils

Ramasamy, Ravichandran, PhD

Biochemistry and Molecular Pharmacology (Medicine-Pharmacology)

Understand the metabolic basis of ischemic injury and heart failure

Rostagno, Agueda, PhD Pathology Cerebrovascular amyloidosis; cerebral hemorrhage; dementia

Ryoo, Hyung Don, PhD Cell Biology The mechanism of caspase regulation; how endoplasmic stress (ER-stress) activates apoptosis

Schmidt, Ann Marie, MD

Medicine (Pharmacology, Biochemistry and Molecular Pharmacology, Pathology)

Diabetic complications, Inflammation, signal transduction and RAGE biology

Schneider, Robert, PhD Microbiology (Radiation Oncolology)

Altered regulation of gene expression in carcinogenesis and cell stress

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Schwab, Susan, PhD Pathology (Skirball Institute) Role of S1P and S1P-generating enzymes in tumor growth

Sigurdsson, Einar, PhD Physiology and Neuroscience (Psychiatry)

Pathogenesis, diagnosis and therapy of Alzheimer's, prion diseases, type-2 diabetes and related neurodegenerative and protein conformational disorders

Skok, Jane, PhD Pathology Nuclear organization of immunoglobulin genes; genomic stability

Victor Torres, Ph.D. Microbiology Regulation of Staph aureus virulence factors the host response to infection.

Wilson, Elaine Lyn, PhD Cell Biology (Urology) The biology of stem cells

Wisniewski, Thomas Neurology (Pathology, Psychiatry)

Mechanisms of dementia

Pathobiology & Translational Medicine Clinical & Supporting Faculty

Aliferis, Constantin, MD, PhD

Pathology Health Informatics, Bioinformatics

Galvao Neto, Antonio, MD

Pathology Gastrointestinal Pathology

Hedvat, Cyrus Pathology Molecular pathology, cancer genomics

Heguy, Adriana Pathology Genomic analysis of tumors Loomis, Cynthia, MD, PhD

Pathology (Dermatology, Cell Biology)

Developmental mechanisms in embryonic patterning; bone/skin morphogenesis

Melamed, Jonathan, MD Pathology Prostate cancer, tissue banking, immunohistochemistry, quality assurance

Neubert, Thomas, PhD Biochemistry and Molecular Pharmacology (Skirball-Pharmacology)

Using mass spectrometry to study proteins and their posttranslational modifications

Polsky, David, MD, PhD Dermatology (Pathology) Melanoma, Cell cycle, Oncogenes, Tumor suppressor genes, p53, MDM2, BRAF

Rapkiewicz, Amy MD Pathology Pathology, Medical Education, Autopsy

Rosenthal, Pamela MD Medicine Rheumatology, Medical Education

Snuderl, Matija, MD Pathology Neuropathology, Molecular Pathology and Epigenetics

Zagzag, David, MD, PhD Pathology (Neurosurgery) Angiogenesis, vasculogenesis, brain tumors, extracellular matrix

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Pathobiology & Translational Medicine Program Curriculum Outline

Our training program is unique at NYUSoM in that, in addition to the formal Basic Science Curriculum (including dissertation research project) required of all Sackler Institute graduate students, we have developed an Integrated Basic Science and Translational Medicine Curriculum and Clinical Curriculum. The Integrated Basic Science and Translational Medicine Curriculum includes the Pathobiology & Translational Medicine program-specific courses, all tightly interwoven with the Clinical Curriculum. In the program components of the Clinical Curriculum, students are exposed to didactic, seminar-based and patient-oriented clinical orientation sessions in order to thoroughly familiarize the student with the human pathology, human pathophysiology, clinical presentation and clinical health consequences, and basic management. By year 3, these sessions become focused on their translational cluster area of interest.

For additional information about the Pathobiology and Translational Medicine program, please visit: http://www.med.nyu.edu/pathology/education/graduate-programs/pathobiology-and-translational-medicine-training-program http://www.med.nyu.edu/sackler/phd-program/training-programs/pathobiology-translational-medicine

Basic Science

Curriculum

Clinical

Curriculum

• Foundations of Cell &

Molecular Biology I

• Scientific Methods

• Responsible Conduct

of Research

• Three Lab Rotations

•

•

Gross Pathology &

Virtual Microscope

Autopsy Sessions

Integrated

Basic Science &

Translational

Medicine

Curriculum

• Introduction to Tissues

& Organ Systems

•

Advanced Tissues &

Organs

• Clinical Correlations Sessions

• Clinical Debriefing Sessions

• Autopsy Sessions

• Introduction to Biostatistics

• Work-in-Progress Seminars

• Grant Writing for Scientists

• Thesis Research

• Elective Courses

Year 1 Year 2 Years 3-4-5

• Thesis Research

• Work-in-Progress Seminars

• Ethics Refresher (Year 5)

• Individual Development

Plans

• Molecular Pathology in the

Omics Era

•

• Seminars & Conferences

• Translational Science &

Medicine Journal Club

• Human Clinical Cluster-Based

Disease Seminars

• Seminars & Conferences

• Gross Pathology & Virtual

Microscope

• Autopsy Sessions

Advanced Tissues &

Organs

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Introduction to Tissues and Organ Systems Course Director: Cynthia Loomis, M.D., Ph.D. Cynthia.loomis@nyumc.org

Course Co-Directors: Eva Hernando, Ph.D.

Eva.hernando@nyumc.org Antonio Neto Galvao

Antonio.GalvaoNeto@nyumc.org Lecture, Discussion and Lab course Time: Fall Semester Course: BMSC-GA 4406 Credits: 4 Overview: This introductory course, specifically designed for Pathobiology graduate students, covers selected topics of tissue organization, anatomy, physiology, immunology and pathology. The goal is to provide a conceptual framework and basic vocabulary that will allow biomedical research scientists to pursue disease-oriented research topics and more effectively employ animal models of disease. In particular, this overview familiarizes students with fundamental principles of how mammalian organisms function physiologically in normal and diseased states. The course is directed by Cindy Loomis and consists of bi-weekly lectures, labs and discussion sessions, which are given by a mixture of clinical, translational, and basic science faculty. This lab sessions are closely coordinated with the lectures and designed to give students first-hand experience examining and distinguishing features of both normal and diseased tissues from clinical (human) and animal (primarily rodent) models. Organization: The course is divided into three modules. The first provides an overview of normal anatomy, tissue histology, and physiology. The lab sessions focus on 1) identifying basic tissue types and organ structures; 2) proper use of the light microscope and other equipment; and 3) standard histological methods. The primary emphasis is on mouse model systems and takes place in the Research Histopathology Core Laboratories. Students will learn to perform basic mouse necropsies as well as to fix, process, embed and examine tissues microscopically. They will obtain a working knowledge of all standard protocols used in tissue preparation and the potential pitfalls of each technique. The second segment of the course defines the general pathological processes that alter the normal or healthy state during clinical disease. The laboratory sessions in this segment focus on clinically relevant (human) histopathology under the guidance of Dr. Antonio Neto Galvao and fellow surgical pathologists. The labs take place in the surgical pathology facilities at Tisch and Bellevue Hospitals. Students will be taught in small groups either at the multi-headed microscope or through innovative digital virtual microscope modules. Students will also visit the surgical pathology bench and will have the option to observe at least one autopsy. Pathology specimens will be used to illustrate features of pathogenesis, with special emphases on cancer and inflammation. The third segment of the course emphasizes a few simple organ systems and major relevant diseases. During this last segment, students will participate in the instructional component of the course, giving a 10-minute powerpoint presentation on a specific organ and relevant disease process. In most cases,

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the presentation topic corresponds to the organ system that the student prepared for histological analysis in the first half of the accompanying lab course (Introduction to Histopathology). Examinations and other requirements: Final evaluations are based on: 1) active class participation; 2) a short powerpoint instructional presentation on a specific organ system; and 3) final take-home essay and digital histopathology lab exam. Required textbooks (DO NOT PURCHASE): Robbins and Cotran, Pathologic Basis of Disease; Kumar, Abbas, Fausto, Elsevier Saunders, 2005. Optional textbooks: Basic Histology: text and atlas. 11th Ed. , L.C. Junqueira, J. Carneiro. McGraw-Hill, 2005. Grant’s Atlas of Anatomy, 11th Ed. A.M.R. Agur, A.F. Dalley. Lippincott, Williams & Wilkins.

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Introduction to Tissues and Organ Systems - Outline

8/18/15

!Introduction!to!Tissues!and!Organ!Systems!Course!5!Fall!2015Course #: G16.4406 4!Credits Tentative(Schedule:((Revised(8.12.15Tentative!Syllabus!

DO!NOT!BUY!BOOKS!BEFORE!FIRST!CLASSProfessors Dr.!Cindy!Loomis Dr.!Eva!Hernando !Location: MSB(598 Smilow(305Contact!Number: 646A732A5828 212A263A9054

Administrative!Support Kristine!Lluveras !Location: MSB(598 (Contact(Number 212A263A3152 (

Primary!Textbook Robbins(Basic(Pathology W.B(Saunders(Company

Optional(Textbooks Netters(Clinical(Anatomy John(T(HansenTextbook(of(Medical(Physiology Guyton,(Arthur(CWheaters(Functional(Histology Barbara(Young

Week Day Date Time Topic Instructor Location

1 Thurs 9/3/14 12:00A2:00 Basic(Org.(of(Simple(Organs(I Loomis Smilow(301

2 Tues 9/8/15 12:00A2:00 Anatomical(Relationships(I Loomis Smilow(301Thurs 9/11/14 12:00A2:00 Mouse(necropsy(lab Loomis( MSB(598((Histo(Core)

3 Tues 9/15/15 ALL(DAY Rosh(Hoshannah XXXXXXXX XXXXXXXXThurs 9/17/15 12:00A1:30 Anatomical(Relationships(II Loomis Smilow(301

4 Tues 9/22/15 12:00A2:00 Basic(org(of(simple(organs(II Loomis Smilow(301 (Thurs 9/24/15 12:00A2:00 Histology(lab Loomis MSB(598((Histo(Core)

5 Tues 9/29/15 12:00A2:00 Review(of(normal(tissue(morphology(&(function Loomis Smilow(301Thurs 10/1/15 12:00A2:00 Basic(Physiology Loomis Smilow(301 (

( ( (6 Tues 10/6/15 12:00A2:00 Cell(Renewal Hernando Smilow(301

Thurs 10/8/15 12:00A2:00 Immunohistochemistry(lab Chiriboga Smilow(301(&(IHC(lab(

7 Tues 10/13/15 12:00A2:00 Cell(Death/Adaptions Hernando Smilow(301 (Thurs 10/15/15 12:00A2:00 Cell(renewal(and(death(lab( Galvao Tisch(444((multiAheaded(scope) (

8 Tues 10/20/15 12:00A2:00 Inflammation( Sun Smilow(301Thurs 10/22/15 12:00A2:00 Inflammation(lab Sun Tisch(444((multiAheaded(scope)

( ( (9 Tues 10/27/15 12:00A2:00 Medical(Imaging Collins Smilow(301

Thurs 10/29/15 12:00A2:00 Endogenous(Causes(of(Disease((Basic(Genetics) Snuderl Tisch(444((multiAheaded(scope)(

10 Tues 11/3/15 12:00A2:00 Hemostasis,(Thrombosis(&(Embolism Melamed Smilow(301 (Turs 11/5/15 12:00A2:00 Hemostasis,(Thrombosis(&(Embolism(lab Melamed Tisch(444((multiAheaded(scope) (

( ( ( (11 Tues 11/10/15 12:00A2:00 Neoplasia(I Hernando( Smilow(301

Thurs 11/12/15 12:00A2:00 Neoplasia(II Hernando( Smilow(301( ( ( (

12 Tues 11/17/15 12:00A2:00 Neoplasia(lab Snuderl Tisch(444((multiAheaded(scope) (Thurs 11/19/15 12:00A2:00 Body(surfaces:((Skin(&(Cornea( Loomis Smilow(301( ( ( ( ( ( (

13 Tues 11/24/15 12:00A2:00 Gastrointestinal(tract Xu Smilow(301Thurs 11/26/15 All(Day Thanksgiving XXXXXXX XXXXXXX

( ( ( (14 Tues( 12/1/15 12:00A2:00 Tissue(presentations(1 Students/Loomis Smilow(301

Thurs 12/3/15 12:00A2:00 Tissue(presentations(2 Students/Loomis Smilow(301( ( ( (

15 Tues 12/8/15 12:00A2:00 Tissue(presentations(3 Students/Loomis Smilow(301Thurs 12/10/15 12:00A2:00 Review Loomis/Galvao Smilow(301 (

16 TBA TBA TBA Autopsy(viewing Melamed/Galvao TBA

17 Tues 12/15/15 12:00A2:00 Review/Take(home(exam Loomis/Galvao Smilow(301

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Advanced Tissues and Organ Systems Course Director: Stefan Feske, M.D

Stefan.feske@nyumc.org Lectures, Small group discussions, Laboratory sessions Time: Spring Semester Course: BMSC-GA 4410

BMSC-GA 2017 BMSC-GA 4464

Credits: 2 credits for each module Overview: This course is a continuation of the “Introduction to Tissues and Organs” course taught in the fall. The goals are to understand the individual organ systems as well as their interactions with other systems, their pathophysiology and the resulting impact on the function or dysfunction of the organism as a whole. The course consists of three modules: 1) cardiovascular and pulmonary system; 2) genito-urinary system (includes kidney), endocrine and autoimmune disorders; and 3) central and peripheral nervous systems. The modules alternate each year such that all three modules are offered over a 2-year cycle. Two of the three modules are required for all students in the Pathobiology Program. Prerequisites for the Advanced Tissues and Organs modules are successful completion of the introductory course or permission by the instructors. The general course structure pairs up, in the same week, a lecture by a faculty member with the discussion of a research paper on the same topic. Paper discussions are led by one student each week who picks his/her topic at the beginning of the semester and identifies – together with the lecturer – a specific paper for discussion. The student gives a brief introduction on the topic and leads the discussion. The presenting student will write a report summarizing and critiquing the paper (due 2 weeks after class). Each student is expected to have read the papers ahead of time and participate in the discussion. – The laboratory sessions will provide a more robust, 3-dimensional understanding of normal organ function as well as better conceptualization of the underlying cellular processes leading to disease. At the end of the semester students write a final exam in the form of a fellowship proposal on a topic related to the material covered during the semester. First year students write a 1-page proposal outlining rational and specific research aims; second year students write a 6-page research grant. The purpose of this exam, together with the paper discussions, is to train students to critically evaluate cutting-edge research and to formulate their own ideas into a viable research project. The final course grade is a composite of active participation throughout the course, the paper presentation & report and the written exam.

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Advanced Tissues and Organ Systems - Outline

Cardiovascular Lecture: Basic Cardiovascular function and anatomy Jan – Feb Lecture: Cardiovascular pathology Spring 2015 LAB: Basic cardiology

Lecture: Cardio-respiratory dysfunction Lecture: Cardio-renal dysfunction LAB: Pediatric cardiology/cardio-resp dysfunction

Endocrine Lecture: Basic Endocrine anatomy and function March - May Lecture: Endocrine pathology Spring 2015 LAB: Basic endocrine

Lecture: Endocrine/bone dysfunction LAB: endocrine

Nervous system Lecture: Basic central nervous system anatomy and function March -- May Lecture: Central nervous system pathology Spring 2016 LAB: central nervous system Special Topics Lecture: Basic peripheral nervous syst. anatomy, function & dysfunction

LAB: peripheral nervous system Lecture: Midterm Presentation/Exam

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MOLECULAR PATHOLOGY IN THE OMICS ERA Course Director: Adriana Heguy, Ph.D. Adriana.Heguy@nyumc.org Lectures, Student Presentations, Discussions Time: Spring Semester Course: Lecture and Small Group Discussions Credits: 3 Overview: Molecular Pathology lies at the crossroads between basic science and clinical medicine. Both the research and clinical aspects of this field have been drastically changed first by the advent of classical molecular biology techniques such as cloning and PCR, and subsequently by the development of genome-wide techniques such as microarrays and deep sequencing. This new paradigm generates massive amounts of genome-wide data and thus bioinformatics and systems biology are a key component of molecular pathology in the post-genomic era. This course intends to get the students familiarized with the genomics and proteomic technologies used in molecular pathology to advance our knowledge of the mechanisms underlying human diseases and disease susceptibility, and to create better diagnostic and prognostic tools using genomic data. This course will cover genomics, proteomics and other “big data”-generating technologies, as well as the bioinformatic approaches relevant to both the research and applied aspects of molecular pathology. The course will relate mostly to cancer and its pathogenesis, as molecular pathology is advancing most rapidly in this field, leading to personalized medicine and the use of genomics in clinical settings.. The lecture/discussion format will give students both a broad background and the opportunity to apply critical thinking skills to recent data in the field. Examinations and other requirements: Class participation in the Discussion sections and a final, take home exam will be used for grading. Students will be expected to read the papers for discussion prior to class and to give presentations of the relevant articles, including methods and supplementary material. The final exam will be in the format of a short proposal describing the use of genomics and/or proteomics in elucidating the mechanisms underlying a specific human disease, and how to derive genomic or proteomic-based assays for clinical diagnostic, prognostic, or treatment-guidance purposes. Students are encouraged to describe a main approach as well as secondary, alternative approaches, and the advantages or pitfalls of each approach. Papers must be written independently, but students are encouraged to discuss the proposed approaches with faculty and/or classmates. Limit is 5 pages (not including references). Include relevant background, experimental design and methods, expected results and interpretation, alternative possible results and interpretation, and references. Be sure that the rationale for your choice of experimental design and methods is clear to the reader. Resources: No textbook is available, as can be expected in this very new, fast-moving field. Please consult the course website on ALEX (https://alex.med.nyu.edu) for course materials. Useful comprehensive high-quality review articles with be provided by individual lecturers.

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MOLECULAR PATHOLOGY IN THE OMICS ERA - Outline

Week Subject Description Faculty member/instructor

1 Sample processing

Acquisition and processing of human samples: regulatory and practical issues. Will cover IRB, biospecimen banking and databases Rachel Brody

1 Sample processing Literature discussion class based on topics from previous lecture Rachel Brody

2 Basic genomic technologies

Next generation sequencing and other genomic based technologies: basic concepts and methodologies Adriana Heguy

2 Genomics/Bioinformatic resources Guided visit to the Genome Technology Center Adriana Heguy

3 Germline genomics

The genetic basis of disease susceptibility: high throughput genotyping and genome-wide association analysis (GWAS) Tomas Kirchhoff

3 Germline genomics Literature discussion class based on topics from previous lecture Tomas Kirchhoff

4 Familial cancer syndromes

Sporadic and inherited mutations in tumors of the nervous system: genetics, genomics, molecular pathways and novel therapies Matthias Karajannis

4 Familial cancer syndromes

Literature discussion class based on topics from previous lecture Matthias Karajannis

5 Copy number variants

Copy number variants in the human genome: from karyotypes and in situ hybridization to array CGH and whole genome sequencing Matija Snuderl

5 Copy number variants

Literature discussion class based on topics from previous lecture Matija Snuderl

6

Structural variants & mutation detection in a clinical setting

Diagnostic testing based on cytogenetic abnormalities and mutation detection in cancer Cyrus Hedvat

6

Structural variants & mutation detection in a clinical setting

Literature discussion class based on topics from previous lecture Cyrus Hedvat

7 Cancer genomics and bioinformatics

Somatic evolution in cancer: algorithms to distinguish “driver” vs. “passenger” mutations or alterations detected by whole genome or whole exome sequencing Kasthuri Kannan

7 Cancer and bioinformatics

Literature discussion class based on topics from previous lecture Kasthuri Kannan

8 Epigenomics Dissecting the epigenome: DNA methylation and chromatin-based approaches Steven Shen

8 Epigenomics Literature discussion class based on topics from previous lecture Steven Shen

9 Chromatin and nuclear architecture

Three-dimensional genome organization and its impact on gene regulation: from single cell microscopy through to genome-wide analysis using deep sequencing Jane Skok

9 Chromatin and nuclear architecture

Literature discussion class based on topics from previous lecture Jane Skok

10 Transcriptomics/ gene expression

Transcriptome profiling and applications in clinical study: an overview and comparison of microarray and RNAseq technology and data analysis Jinhua Wang

10 Transcriptomics/ gene expression

Literature discussion class based on topics from previous lecture Jinhua Wang

11 Pathway analysis Bioinformatic approaches to identify key pathways in human disease Aris Tsirigos

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10 For final exam Assignment of disease problem for final paper Heguy/Shen

11 Microbiome and metagenomics

Human microbiome and metagenomics as a diagnostic/ prognostic tool Martin Blaser

11 Microbiome and metagenomics

Literature discussion class based on topics from previous lecture Martin Blaser

12

Integrated approaches to “omics” data

Multi-omics integration in cancer: data analysis in the context of TCGA David Fenyo

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Integrated approaches to “omics” data

Literature discussion class based on topics from previous lecture David Fenyo

13 Proteomics Epithelial stem cells - Skin and intestine Beatrix Ueberheide

13 Proteomics Literature discussion class based on topics from previous lecture Beatrix Ueberheide

14 Imaging and visual technologies

Translating qualitative visual information into quantitative data: image analysis strategies for quantifying different types of microscopy data

Cindy Loomis/ Michael Cammer

14 Imaging and visual technologies

Literature discussion class based on topics from previous lecture

Cindy Loomis/ Michael Cammer

15 Ethics Ethical issues in human genomics data Arthur Caplan

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Work-in-Progress – 2013-2014 series October 23, 2014

Laura Fogli The role of Th17 cells in airway inflammation

October 30, 2014

Erwin Cabrera N- and C-terminate truncated amyloid beta species: footprints of clearance mechanisms or key elements in the process of amyloidogenesis

November 6, 2014

Eric Schafler Roles of ART-27 during spermatogenesis

November 13, 2014

Monique Foster EHD2 stabilizes the surface expression of KATP channels

November 20, 2014

Michael Gonzalez Characterizing the role of TMEM26 in the function of alternatively activated macrophages

December 4, 2014

Anjelique Schulfer Determining the role of intact immunity in developing microbe-induced obesity

December 11, 2014

Krystal Herline Immunomodulation targeting pathology associated protein conformers in 3xTg and TgSwDI mice

January 15, 2015

Krystal Sotolongo The role of metabolic stress and amyloid β peptide on synaptic and mitochondrial function: Implications for the pathogenesis of Alzheimer’s disease

January 22, 2015

Evelyn Litwinoff The Role of RAGE & Autophagy in Obese Adipose Tissue Inflammation

February 5, 2015

Emilie Montenont The contribution of platelet transcriptome to platelet activity

February 10, 2015

Julie Diamond Role of irradiated tumor-derived exosomes in immune responses to breast cancer

February 19, 2015

Elisa Araldi Modulation of cholesterol synthesis affects inflammation in macrophages

March 10, 2015

Laura Senatus Receptor for Advanced Glycation End Products (RAGE) and Impaired Regression of Diabetic Atherosclerosis

March 19, 2015

Eric Schafler “SCML2 Establishes the Male germline Epigenome through Regulation of Histone H2A Ubiquitination”

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March 26, 2015

Anjelique Schulfer "Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation"

April 2, 2015 Erwin Cabrera "Scanning ultrasound removes amyloid-b and restores memory in an Alzheimer’s disease mouse model"

April 16, 2015

Krystal Herline "BMI and risk of dementia in two million people over two decades: a retrospective cohort study"

April 23, 2015

Krystal Sotolongo “Fyn inhibition rescues established memory and synapse loss in Alzheimer mice.”

April 30, 2015

Evelyn Litwinoff "Brown adipose tissue transplantation reverses obesity in ObOb mice"

May 21, 2015

Michael Gonzalez "Chronic helminth infection and helminth-derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice"

May 28, 2015

Laura Senatus "Human Aldose Reductase expression accelerates diabetic atherosclerosis in transgenic mice"

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Pathobiology & Translational Medicine Training Program

Third Annual Retreat May 12, 2015

11:45-12:45 PM Opening Luncheon - MSB 588 12:45– 5:00 PM Smilow Multi-Purpose Room, First Floor 12:45 PM Welcome by Dr. Ann Marie Schmidt 1:00-1:40 PM Dr. Adrian Erlebacher, Associate Professor, Dept. of Pathology

A novel role for neutrophils in combating cancer 1:40 PM Session 1 : Moderated by Dr. Cindy Loomis 1:40-2:00 PM Kayan Tam, Mentor Dr. Victor Torres

Structure-Function Relationship Between a Staphylococcus aureus Leukocidin and its Host Receptor During Leukocidin-Mediated Cytotoxicity

2:00-2:20 PM Larua Fogli, Mentor Dr. Sergei Koralov The Role of Th17 Cells in Bone Loss 2:20-2:40 PM Erwin Cabrera, Mentor Dr. Jorge Ghiso

N- and C-terminal Truncated Amyloid Beta Species: Footprints of Clearance Mechanisms or Key Elements in the Process of Amyloidogenesis?

2:40-3:00 PM Break 3:00 PM Session 2: Moderated by Dr. Jorge Ghiso 3:00-3:40 PM Dr. Daniel Ceradini, Assistant Professor, Dept of Plastic Surgery

ROS in translation: Therapeutic targeting of redox homeostasis to prevent diabetic vascular complications

3:40-4:00 PM Evelyn Litwinoff, Mentor Dr. Ann Marie Schmidt The Effect of RAGE on Autophagy in Diet Induced Obesity Driven Adipose Tissue Inflammation

4:00-4:20 PM Eric Schafler, Mentor Dr. Susan Logan ART-27 Regulates Spermatogonial Stem Cell Differentiation and Sertoli Cell Functions in the Mouse Testis

4:20-4:50 PM Julie Diamond, Mentor Dr. Sandra DeMaria Ionizing Radiation Modifies the Molecular Composition of Exosomes Derived from Breast Cancer Cells

5:00-6:00 PM Poster Session (Wine and Cheese) Alumni Hall

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Poster Session Presentations Elisa Araldi, Mentor Dr. Yajaira Suarez Modulation of cholesterol metabolism decreases inflammatory responses in macrophages Julia Derk, Mentor Dr. Ann Marie Schmidt RAGE Signal Transduction & Implications for Neuroinflammation in Alzheimer's Disease Research Michael Gonzalez, Mentor Dr. P’ng Loke Conversion of monocyte derived M2 macrophages into a tissue resident macrophage phenotype Krystal Herline, Mentor Dr. Thomas Wisniewski Characterization of a Novel Monoclonal Antibody Targeting Pathological Proteins in Alzheimer’s Disease Lena Lau, Mentor Dr. Gregory David The Role of Th17 Cells in Bone Loss Emillie Montenont, Mentor Dr. Jeffrey Berger The role of WDR1 in platelet function Anjelique Schulfer, Mentor Dr. Martin Blaser Cohousing mice after low-dose antibiotic exposure to change body composition Laura Senatus, Mentor Dr. Ann Marie Schmidt Receptor for Advanced Glycation End Products (Ager) and Diaphanous-1 (Drf1) Suppress Macrophage Reverse Transendothelial Migration and Regression of Diabetic Atherosclerosis Krystal Sotolongo, Mentor Dr. Jorge Ghiso Synergistic effect of metabolic stress on Aβ-mediated synaptic and mitochondrial dysfunction