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Research Areas of Interest

Photo of a microscopic crystalAnti-infectives & Drug Discovery

Academia is playing an increasingly important role in the development of new antimicrobial drugs, as reflected by the recent creation of the new National Center for Advancing Translational Sciences (NCATS) at NIH. URMC faculty are involved in the identification of new genetic targets for antimicrobial drugs, and in the development and early-phase testing of new anti-infectives for hard-to-treat organisms such as Methicillin Resistant Staphylococcus Aureus (MRSA) and Acinetobacter baumanii, as well as TB and fungal pathogens that afflict immunocompromised persons.

Active Researchers

  • Stephen Dewhurst - HIV Vaccine and Microbicide Development; Novel Therapeutics for NeuroAIDS; Role of Cellular Factors in Influenza Virus Pathogenesis and Host Adaptation
  • Paul Dunman - Characterizing the S. aureus factors that influence Staphylococcus aureus' ability to cause disease, as well as define the regulatory mechanism(s) that modulate the expression of these genes.
  • Constantine Haidaris - Pathogenesis of Pneumocystis carinii and Candida albicans
  • Baek Kim - HIV Reverse Transcriptase: Role in Viral Evolution, Mutagenesis and Cell Type Specificity;Evolution of Influenza Virus and Viral RNA Polymerase.
  • Minsoo Kim - T cell migration and autoimmune disease/ Inflammation biology of sepsis
  • Michael Koo - The role of extracellular polysaccharide matrix in the pathogenicity of oral biofilms
  • Damian Krysan - Identifying new cell wall-specific antifungal drug targets.
  • Sanjay Maggirwar - Role of NF-kB in Cell Growth and Survival
  • Luis Martinez-Sobrido - Evasion of the innate immune response by viruses
  • Joshua Munger - Mechanisms of Viral and Oncogenic Metabolic Manipulation
  • Martin Pavelka - Cell envelopes of pathogenic bacteria.
  • Robert Quivey - Stress-adaptive gene expression in the oral pathogen, Streptococcus mutans

An electron micrograph of a Vaccinia virus.Autoimmunity

Autoimmune disease is an important and growing health concern, playing a central role in diseases such as diabetes, lupus, multiple sclerosis and rheumatoid arthritis. The URMC is home to one of only 9 national Autoimmunity Centers of Excellence (ACE) and faculty research emphasizes immune mechanisms in diabetes, lupus, rheumatoid arthritis, and more. This research is combined with fundamental studies on both B- and T- cell subsets, including regulatory T cells.

Active Researchers

  • Deborah Fowell - Regulation of Immunity
  • Michael Elliott - Phagocytic clearance of apoptotic cells: molecular regulation and immunological consequences
  • Minsoo Kim - T cell migration and autoimmune disease/ Inflammation biology of sepsis
  • Sanjay Maggirwar - Role of NF-kB in Cell Growth and Survival
  • Andrea Sant - Class II Restricted Antigen Presentation.
  • Eddie Schwarz - Molecular Mechanisms and Gene Therapy for Arthritis.

Highly-magnified, digitally-colorized transmission electron micrograph (TEM) depicted numbers of virions from a Novel Flu H1N1 isolateBiodefense & Respiratory Pathogens

Faculty research focusses on a range of Category A, B and C Priority Pathogens. Studies include analysis of the pathogenesis of important bacterial and viral biodefense agents, comparative genomic studies on Vibrio species, genetic analysis of Francisella tularensis and vaccinia virus (which is a safe experimental model for smallpox), analysis of immune responses to such viruses as influenza virus (flu) and Respiratory Syncytial Virus (RSV), and the development and testing of new vaccines for diseases such as anthrax, botulism, and smallpox. In conjunction with faculty in several different Centers and Departments, there is a strong emphasis on respiratory pathogens, including Francisella tularensis, flu, Pneumocystis carinii and RSV. Finally, the URMC is home to one of only 5 national Centers for Excellence for Influenza Research and Surveillance (CEIRS), the New York Influenza Center of Excellence. (NYICE)

Active Researchers

  • John Frelinger - T cell immunity to tumors and pathogens.
  • Francis Gigliotti - Immunopathogenesis of Pneumocystis carinii Pneumonia
  • Paige Lawrence - Environmental influences on immune system developmental programming and function
  • Sanjay Maggirwar - Role of NF-kB in Cell Growth and Survival
  • Luis Martinez-Sobrido - Evasion of the innate immune response by viruses
  • Joshua Munger - Mechanisms of Viral and Oncogenic Metabolic Manipulation
  • Martin Pavelka - Cell envelopes of pathogenic bacteria.
  • Richard Phipps - B Cells and Prostaglandins; Fibroblasts as Effector Cells in Immunity.
  • Andrea Sant - Class II Restricted Antigen Presentation.
  • Toru Takimoto - Molecular Mechanisms of Paramyxovirus Infection, Replication and Assembly.
  • Brian Ward - Molecular Mechanisms of Poxvirus Envelope Formation.

Photo courtesy of the NIH image bank.Cancer

Oncogenically transformed cells arise through a multistep process, and are normally subject to immune surveillance and elimination by the immune system. Cluster research focuses understanding of the immune mechanisms involved in tumor recognition and rejection, as well as fundamental mechanisms of cellular transformation and the role of microbial populations in head-and-neck cancer. Studies include translational research aimed at improved cancer therapeutics, as well as studies into the basic mechanisms of cell transformation.

Active Researchers

  • Michael Elliott - Phagocytic clearance of apoptotic cells: molecular regulation and immunological consequences
  • Steven Gill - Molecular basis of Staphylococcus aureus pathogenesis / Modulation of human health and disease by the human microbiome
  • John Frelinger - T cell immunity to tumors and pathogens.
  • Edith Lord - Cell Mediated Immunity to Tumors.
  • Sanjay Maggirwar - Role of NF-kB in Cell Growth and Survival
  • Joshua Munger - Mechanisms of Viral and Oncogenic Metabolic Manipulation
  • Richard Phipps - B Cells and Prostaglandins; Fibroblasts as Effector Cells in Immunity.
  • Jacques Robert - Evolution of Tumor Immunity; Tumorigenesis and Immune Surveillance
  • PJ Simpson-Haidaris - Innate Immunity and Inflammation in Breast Cancer Metastasis>

Neuron from a crab showing the cell body (bottom), axon (rope-like extension), and growth cone (top right)Cell Biology

Microbes and viruses interact with host cells to induce alterations in cellular phenotype and function, thereby subverting host cell metabolism to meet their own needs. In addition, many microbes and viruses exert effects on the host immune response, so as to evade host immune control. Knowledge of the interplay between infectious pathogens and their host cells is therefore important, in order to identify potential new targets for drug therapy and as a basis for understanding microbial pathogenesis. Research focuses on various aspects of mammalian and amphibian cell biology including, cell to cell interactions, cell cycle control, intracellular signaling, differentiation and subcellular organelles.

Active Researchers

  • Deborah Fowell - Regulation of Immunity
  • Michael Elliott - Phagocytic clearance of apoptotic cells: molecular regulation and immunological consequences
  • Minsoo Kim - T cell migration and autoimmune disease/ Inflammation biology of sepsis
  • Damian Krysan - Identifying new cell wall-specific antifungal drug targets.
  • Paige Lawrence - Environmental influences on immune system developmental programming and function
  • Jim Miller - Molecular and Cellular Events That Regulate T Cell Signaling and Activation
  • Joshua Munger - Mechanisms of Viral and Oncogenic Metabolic Manipulation
  • Brian Ward - Molecular Mechanisms of Poxvirus Envelope Formation.

Photo Credit: H.D.A Lindquist, U.S. EPAESKAPE Pathogens, Hard-To-Treat Infections & Drug Resistant Organisms

The ESKAPE pathogens comprise the 6 bacterial pathogens considered to be of greatest healthcare concern by the Infectious Diseases Society of America, because of their high burden of disease and frequent ability to evade currently used antibiotics. Chief among these is Staphylococcus aureus, which is the focus of several faculty laboratories, interested in establishing bacterial determinants of virulence as well as new targets for antimicrobial therapy. Other ESKAPE pathogens under investigation include Acinetobacter baumanii, Pseudomonas aeruginosa and enterobacterial species. Additional research focuses on Mycobacterium tuberculosis, as well as fungal species that a major cause of disease among medically immune suppressed persons, and polymicrobial infection.

Active Researchers

  • Jacqueline Abranches - dissecting, at the molecular level, the interactions between S. mutans and Human Coronary Endothelial Cells.
  • Paul Dunman - Characterizing the S. aureus factors that influence Staphylococcus aureus' ability to cause disease, as well as define the regulatory mechanism(s) that modulate the expression of these genes.
  • Steven Gill - Molecular basis of Staphylococcus aureus pathogenesis / Modulation of human health and disease by the human microbiome
  • Constantine Haidaris - Pathogenesis of Pneumocystis carinii and Candida albicans
  • Damian Krysan - Identifying new cell wall-specific antifungal drug targets.
  • José Lemos - Molecular Genetics and Physiology of the Response to Environmental Stresses by Oral Bacteria.
  • Martin Pavelka - Cell envelopes of pathogenic bacteria.
  • Eddie Schwarz - Molecular Mechanisms and Gene Therapy for Arthritis.

Untreated cells from children with the genetic disease progeria (left) compared to similar cells treated with farnesyltransferase inhibitors (FTIs). In the test tube, FTIs reverse the nuclear damage caused by the disease.Genetics, Genomics & Metagenomics

Microbes and viruses interact with their immediate environment and in doing so alter the expression of their own genes or those of the host. Faculty study the regulation of gene expression at all levels, including global changes in bacterial gene expression in biofilms and dental caries, cytokine and gene expression changes associated with immune cell differentiation, and the comparative genomics of Vibrio cholerae species. Faculty are also examining how microbes interact at the population level, and how microbial communities contribute to disease; ongoing studies examine the possible role of oral microbial communities in polymicrobial infections and in the development and progression of head-and-neck cancers. These studies are enhanced by the University of Rochester's state of the art Functional Genomics Center, and other recent upgrades in the Core Facilities of the Medical Center.

Active Researchers

  • Jacqueline Abranches - dissecting, at the molecular level, the interactions between S. mutans and Human Coronary Endothelial Cells.
  • Scott Butler- Post-transcriptional Regulation of mRNA Expression in the Nucleus of Eukaryotic Cells.
  • Michelle Dziejman- Type Three Secretion System mediated pathogenesis of V.cholerae.
  • Steven Gill - Molecular basis of Staphylococcus aureus pathogenesis / Modulation of human health and disease by the human microbiome
  • José Lemos - Molecular Genetics and Physiology of the Response to Environmental Stresses by Oral Bacteria.
  • Joshua Munger - Mechanisms of Viral and Oncogenic Metabolic Manipulation
  • Martin Pavelka - Cell envelopes of pathogenic bacteria.
  • Robert Quivey - Stress-adaptive gene expression in the oral pathogen, Streptococcus mutans
  • Jacques Robert - Evolution of Tumor Immunity; Tumorigenesis and Immune Surveillance

AIDS virus (HIV). computer model produced by Richard FeldmannHIV / AIDS

HIV/AIDS remains a major cause of death both in the U.S. and internationally.
Faculty research on HIV/AIDS includes studies on: viral replication and reverse transcription; viral pathogenesis, including HIV-associated neurologic disease; development of novel therapeutic and preventive approaches – including new drugs, microbicides and vaccines; and studies on the opportunistic pathogens that are a major cause of morbidity and mortality in persons with HIV/AIDS. The University of Rochester Developmental Center for AIDS Research provides a central hub for campus research on the virus.

Active Researchers

  • Stephen Dewhurst - HIV Vaccine and Microbicide Development; Novel Therapeutics for NeuroAIDS; Role of Cellular Factors in Influenza Virus Pathogenesis and Host Adaptation
  • Harris Gelbard - Effects of HIV-1 infection on neuronal function, signaling, and fate in the CNS.
  • Sanjay Maggirwar - Role of NF-kB in Cell Growth and Survival
  • Joshua Munger - Mechanisms of Viral and Oncogenic Metabolic Manipulation
  • Andrea Sant - Class II Restricted Antigen Presentation.

Magnified 1125X, this thin film photomicrograph of a blood smear, revealed the presence of a leukocyte (white blood cell, WBC) known as a lymphocyte. (CDC/ Dr. Mae Melvin)Immune Regulation & Immunologic Mechanisms

Research into immune regulation and immunological mechanisms includes studies in diverse research areas in immunology, such as: antigen presentation and processing; B cell subsets and regulation of B cell responses; T cell activation and differentiation; T cell memory and homing; regulatory T cells; immune responses to pathogenic organisms; comparative immunology using the frog Xenopus as a model system; and mechanisms involved in the pathogenesis of autoimmune diseases such as diabetes. These varied research programs seek to dissect key regulatory events that control protective and pathogenic immune responses.

Active Researchers

  • Deborah Fowell - Regulation of Immunity
  • Michael Elliott - Phagocytic clearance of apoptotic cells: molecular regulation and immunological consequences
  • John Frelinger - T cell immunity to tumors and pathogens.
  • Harris Gelbard - Effects of HIV-1 infection on neuronal function, signaling, and fate in the CNS.
  • Steve Georas - Mechanisms of allergic inflammation, mouse models of asthma, dendritic cell-T cell cross talk, airway epithelial barrier dysfunction
  • Minsoo Kim - T cell migration and autoimmune disease/ Inflammation biology of sepsis
  • Paige Lawrence - Environmental influences on immune system developmental programming and function
  • Edith Lord - Cell Mediated Immunity to Tumors.
  • Jim Miller - Molecular and Cellular Events That Regulate T Cell Signaling and Activation
  • Shawn Murphy - MHC class II gene expression
  • Richard Phipps - B Cells and Prostaglandins; Fibroblasts as Effector Cells in Immunity.
  • Jacques Robert - Evolution of Tumor Immunity; Tumorigenesis and Immune Surveillance
  • Andrea Sant - Class II Restricted Antigen Presentation.

 the ultrastructural appearance of a single virus particle, or “virion”, of measles virus. (CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.)Molecular Basis of Microbial Pathogenesis

An important weapon in the battle of infectious diseases is a basic understanding of the mechanisms of pathogenesis of infectious agents and the interaction of the pathogen with the host. A major research goal of the faculty is therefore to examine the mechanisms by which pathogenic microorganisms cause disease, using an interdisciplinary approach that involves scientists trained in microbiology, virology, molecular biology, and host defense.

Active Researchers

  • Deborah Fowell - Regulation of Immunity
  • Jacqueline Abranches - dissecting, at the molecular level, the interactions between S. mutans and Human Coronary Endothelial Cells.
  • Scott Butler- Post-transcriptional Regulation of mRNA Expression in the Nucleus of Eukaryotic Cells.
  • Ginny Clark- Regulation of Virulence Factors in Neisseria gonorrhoeae.
  • Stephen Dewhurst - HIV Vaccine and Microbicide Development; Novel Therapeutics for NeuroAIDS; Role of Cellular Factors in Influenza Virus Pathogenesis and Host Adaptation
  • Paul Dunman - Characterizing the S. aureus factors that influence Staphylococcus aureus' ability to cause disease, as well as define the regulatory mechanism(s) that modulate the expression of these genes.
  • Michelle Dziejman- Type Three Secretion System mediated pathogenesis of V.cholerae.
  • John Frelinger - T cell immunity to tumors and pathogens.
  • Francis Gigliotti - Immunopathogenesis of Pneumocystis carinii Pneumonia
  • Steven Gill - Molecular basis of Staphylococcus aureus pathogenesis / Modulation of human health and disease by the human microbiome
  • Barbara Iglewski - Molecular Pathogenesis of Pseudomonas aeruginosa.
  • Michael Koo - The role of extracellular polysaccharide matrix in the pathogenicity of oral biofilms
  • Damian Krysan - Identifying new cell wall-specific antifungal drug targets.
  • José Lemos - Molecular Genetics and Physiology of the Response to Environmental Stresses by Oral Bacteria.
  • Luis Martinez-Sobrido - Evasion of the innate immune response by viruses
  • Joshua Munger - Mechanisms of Viral and Oncogenic Metabolic Manipulation
  • Martin Pavelka - Cell envelopes of pathogenic bacteria.
  • Robert Quivey - Stress-adaptive gene expression in the oral pathogen, Streptococcus mutans
  • Jacques Robert - Evolution of Tumor Immunity; Tumorigenesis and Immune Surveillance
  • Toru Takimoto - Molecular Mechanisms of Paramyxovirus Infection, Replication and Assembly.
  • Brian Ward - Molecular Mechanisms of Poxvirus Envelope Formation.

Under a magnification of 6,408X, this scanning electron micrograph (SEM) depicted spores from the Aimes strain of Bacillus anthracis bacteria.  (CDC/ Laura Rose)Vaccine Biology

Vaccines represent perhaps the most cost-effective approach to improving human health and well-being, saving tens of millions of lives each year. Moreover, the UR has an impressive track record of contributing to the development of important human vaccines, including the Hemophilus influenza b (Hib) vaccine and the recently developed Human Papillomavirus (HPV) vaccine

However, there remains a pressing need for new and improved vaccines for medically important microbial pathogens such as HIV, novel influenza viruses, respiratory syncytial virus (RSV) and more. Research focuses on basic mechanisms involved in the generation of pathogen-specific immune responses as well as translationally-oriented studies that involve the derivation and testing of novel vaccines and/or vaccine delivery systems.

Active Researchers

  • Stephen Dewhurst - HIV Vaccine and Microbicide Development; Novel Therapeutics for NeuroAIDS; Role of Cellular Factors in Influenza Virus Pathogenesis and Host Adaptation
  • Paul Dunman - Characterizing the S. aureus factors that influence Staphylococcus aureus' ability to cause disease, as well as define the regulatory mechanism(s) that modulate the expression of these genes.
  • John Frelinger - T cell immunity to tumors and pathogens.
  • Edith Lord - Cell Mediated Immunity to Tumors.
  • Luis Martinez-Sobrido - Evasion of the innate immune response by viruses
  • Jim Miller - Molecular and Cellular Events That Regulate T Cell Signaling and Activation
  • Jacques Robert - Evolution of Tumor Immunity; Tumorigenesis and Immune Surveillance
  • Andrea Sant - Class II Restricted Antigen Presentation.
  • Eddie Schwarz - Molecular Mechanisms and Gene Therapy for Arthritis.

Magnified 6,740x, this scanning electron micrograph (SEM) depicted a grouping of Ralstonia mannitolilytica bacteria, which was harvested from a pure culture. - CDC/ Judith Noble-Wang, Ph.D.Respiratory Pathogens

Interactions of respiratory pathogens with the host respiratory environment can lead to severe life-threatening infections or chronic debilitating infections that persist for years.  Severe infections are often the result of synergistic interactions between bacterial and viral pathogens such as Staphylococcus aureus and Respiratory Syncytial Virus (RSV).  Chronic lung infections such as Cystic Fibrosis are often polymicrobial infections of multiple bacteria, including Pseudomonas aeruginosa, Hemophilus influenzae and Staphylococcus aureus. Multiple faculty in the department and associated Centers study RSV, influenza virus, Staphylococcus aureus, Pseudomonas aeruginosa, Mycobacterium tuberculosis and Pneumocystis carinii.  Investigators are exploring mechanisms of virulence as well as development of vaccines.  

Active Researchers

  • Stephen Dewhurst - HIV Vaccine and Microbicide Development; Novel Therapeutics for NeuroAIDS; Role of Cellular Factors in Influenza Virus Pathogenesis and Host Adaptation
  • Steven Gill - Molecular basis of Staphylococcus aureus pathogenesis / Modulation of human health and disease by the human microbiome
  • Barbara Iglewski - Molecular Pathogenesis of Pseudomonas aeruginosa.
  • Martin Pavelka - Cell envelopes of pathogenic bacteria.
  • Toru Takimoto - Molecular Mechanisms of Paramyxovirus Infection, Replication and Assembly.

Magnified 15X, this image depicts the morphologic characteristics displayed by two Gram-positive, Actinomyces naeslundi bacterial colonies, of the “smooth” strain, W-1003, which were cultivated on an unknown culture medium. - CDC/ Dr. Lucille K. GeorgOpportunistic Pathogens

Opportunistic pathogens are microorganisms that usually do not cause disease in healthy hosts.  However, they are often the source of opportunistic infections in hosts who are immunocompromised or when they bypass host defenses as a result of tissue damage caused by cuts, burns or surgery.  Faculty research in the department is focused on bacterial and fungal opportunistic pathogens, including Staphylococcus aureus, Acinetobacter baumanii, Enterococcus faecalis, Pneumocystis carinii, Candida albicans and   Cryptococcus neoformans.  Investigators use biochemical, genetic and genomic approaches to study mechanisms of pathogenesis and interactions with the host.  

Active Researchers

  • Jacqueline Abranches - dissecting, at the molecular level, the interactions between S. mutans and Human Coronary Endothelial Cells.
  • Francis Gigliotti - Immunopathogenesis of Pneumocystis carinii Pneumonia
  • Steven Gill - Molecular basis of Staphylococcus aureus pathogenesis / Modulation of human health and disease by the human microbiome
  • Constantine Haidaris - Pathogenesis of Pneumocystis carinii and Candida albicans
  • Damian Krysan - Identifying new cell wall-specific antifungal drug targets.
  • José Lemos - Molecular Genetics and Physiology of the Response to Environmental Stresses by Oral Bacteria.