Michael Pichichero, MD
Director, Rochester General Hospital Research Institute
Dr. Michael E. Pichichero is a physician-scientist, trained and board certified in pediatrics, pediatric infectious diseases and adult and pediatric allergy/immunology. His career has been as a clinical and translational vaccine immunobiologist. He brings the experience of a continuously funded investigator by NIH since 1981. He has received over $70 million in federal, foundation, association and industry grants and he has >300 peer reviewed publications; 150 in the field of vaccines and vaccine immunobiology pertaining to pertussis, diphtheria, tetanus, rotavirus, influenza, tularemia, botulism, and H. influenzae type b, pneumococcal and meningococcal conjugate and candidate nontypeable H. influenzae and S. pneumoniae protein candidate vaccines, and 65 in the field of acute otitis media (AOM). Dr. Pichichero was on the discovery team at the University of Rochester that invented the H. influenzae type b and pneumococcal conjugate vaccines. His role was candidate antigen identification, evaluation of mucosal and serum antibody responses and clinical trial supervision for prototype conjugate vaccines. In 2005, Dr. Pichichero returned to the bench, recruited 3 PhD scientists and a post-doc to launch a focused research team dedicated to vaccine immunobiology in children. He left the Univ. of Rochester in 2009 to accept a new position across town as Director of the Rochester General Hospital Research Institute (RGHRI).
Dr. Pichichero’s lab is focused on prospective, longitudinal clinical and translational studies of acute otitis media (AOM) (R01 DC 08671). His group seeks to define the adaptive and innate immune response deficits among otitis prone (OP) children to infections caused by nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn). They seek to understand the immunity deficits among OP children in the context of overcoming the immune modulating effects of upper respiratory viral infections. To better understand NTHi and Spn pathogenesis and assist in vaccine development they are: (1) identifying specific adaptive immune deficits in OP children; (2) determining independent contributions of mucosal immunity in OP children; (3) understanding the role of innate responses to co-infection of respiratory bacteria and viruses; and (4) defining the role of differences in the nasopharyngeal (NP) inflammatory response in shaping the mucosal microenvironment to allow for NTHi/Spn colonization and then infection.
In 2011, Dr. Pichichero’s group discovered the most common immunodeficiency of children (occurring in about 5% of 6 to 24 month olds) they termed Prolonged Neonatal Immune Profile (PNIP). They found that PNIP children have even lower antibody and antigen-specific memory T-cell responses than normal young children to multiple vaccines. Their immune profile appears similar to neonates, leaving them even more susceptible to multiple vaccine- preventable infections. The differences in the immune responses of PNIP children and normal and other low vaccine responder young children may be attributable to multiple factors. The group plans to further characterize the immunologic differences of adaptive immune responses, interactions among immunity effector cells, and mechanisms that contribute to the more limited immune responses to vaccines in normal, low vaccine responders and PNIP young children. Their focus will be on CD4 T-cell, B cell and APC cell responses with respect to activation, function and long-term persistence (memory) after routine pediatric vaccinations, comparing normal, low vaccine responders and PNIP children. The ultimate goal is to understand the key characteristics of immunity in young children that might be augmented by new rational vaccine design and addition of adjuvants to overcome the lack of response and need for multiple vaccine doses to establish protection from disease and lifelong immunity.
Eugene P. Toy, MD
Chief, Department Obstetrics & Gynecology
Dr. Toy holds a number of positions at Rochester Regional Hospital and maintains academic appointments at University of Rochester and Saba Medical School as a Gynecologic Oncology faculty member within the department of Ob/Gyn. In addition to supervising medical Residents and Fellows, Dr. Toy has had a long standing interest in studying the signaling pathways of ovarian cancer and human papillomavirus (HPV) related cervical carcinogenesis. His early work in the laboratory of Robert Rose, Ph.D. was funded by an R21 grant in the Reproductive Scientist’s Development Program leading to independent funding in novel targets for abrogating HPV viral proliferation and resultant precursor lesions for invasive cervical cancer. Using both in vivo and organotypic culture assays, his investigation of growth potential of cervical tumors led to application of similar paradigm to ovarian cancer. Current work focuses on cofactors including the local microenvironment for tumor growth and the microbiome as it relates to early transformation of precancerous cells.
Brian Poligone, MD, PhD
Research Scientist II
Dr. Poligone was first to discover that dysregulation of NF-κB in dendritic cells can lead to an abnormal immune response and ultimately auto-immunity. His interest as both a Dermatologist and research scientist is in the field of cutaneous lymphoma. Dr. Poligone’s last published work shows that doxycycline induces apoptosis in multiple different cell lines from patients with two common subtypes of Cutaneous T-cell Lymphoma, Mycosis Fungoides and Sézary Syndrome. Doxycycline inhibits TNF induced NF-kB activation and reduces expression of NF-kB dependent anti-apoptotic proteins. He is committed to the study of NF-kB signaling in human disease. He has demonstrated that constitutive phosphorylation of the NF-κB subunit p65 promotes a non-psoriasisiform dermatitis that is also driven by TNF, and hyperplasia leading to the development of pre-malignant keratoacanthoma-like lesions. His current funding is from the National Psoriasis Foundation and the Valeant Investigator Initiated Study.
Lukas Pfannenstiel, PhD Research Scientist I
Dr. Pfannenstiel is a research scientist with a background in tumor biology and cancer immunotherapy and a scientific interest in mechanisms used by tumors to evade the immune system. He trained at Johns Hopkins in the laboratory of Elizabeth Jaffee studying the combination of vaccines and common chemotherapy drugs in a mouse model of breast cancer. At the Cleveland Clinic, he studied a novel population of dysfunctional CD8+ T cells induced by tumors that blunt immune responses against them in both human specimens and mouse models of melanoma and head and neck cancer. He also studied the unique role of a pro-survival gene, Mcl-1, that tumors use to avoid chemotherapy-induced senescence. Current projects include studying the role of the PKK gene in the development of non-melanoma skin cancer using both mouse and human tissue models and the mechanism by which doxycycline preferentially induces cell death in T cell lymphomas.
Robert Zagursky (Zag), PhD
Zag is manager and scientist, trained in the fields of microbiology, immunology, vaccinology, protein structure and bioinformatics. He has 30 years’ of life science experience in industry of which 15 years were in human vaccine discovery at Wyeth/Pfizer where as a Research Fellow he took early retirement. Zag has a number of publications and patents. He currently also holds an appointment in the department of Immunology and Microbiology at URMC. His past research focused on the discovery of vaccine candidates to Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Neisseria meningitidis as well as lead a team in the development of a novel HIV vaccine candidate. Zag was on the discovery team at Wyeth that developed the first Meningococcal Group B Vaccine approved in the USA, Trumenba. He currently supports the daily research operations of the scientists, reviews documents, organizes lab functions and oversees the development of a new clinical/research database.
Ravinder Kaur, PhD
Research Scientist II
Dr. Kaur is a Research Scientist I trained in the fields of microbiology & immunology. Her research focuses on pathogenesis and immunology involving the bacterial pathogens S. pneumoniae and Haemophilus influenzae. Dr. Kaur works with human samples to understand differential expression of virulence determinants by these respiratory pathogens when they colonize the nasopharynx and progress to acute otitis media in children. She seeks to identify whether vaccine candidate proteins of S. pneumoniae and Haemophilus influenzae would be targets for immune responses occurring at the site of colonization compared to the site of infection. The microbiome of the nasopharynx and innate and adaptive immune responses may modulate protein expression by these respiratory bacteria; differences may exist between humans prone to such infections compared to those who resist infection more effectively.
Qingfu Xu, PhD
Research Scientist II
Dr. Xu is a Research Scientist II, trained in the fields of veterinary medicine, animal physiology & biochemistry, cellular & molecular biology and microbiology & immunology. He has had 15 years of research experience with more than 50 publications in peer-reviewed journals. He was working on transcriptional regulation of animal growth hormone receptor gene expression and development of genetic vaccines against potential biodefense agents such as botulism, anthrax, pneumonia and tularemia. His current research interests include (1) mucosa immune response to bacterial pathogens of bacterial respiratory tract infection; (2) bacterial-bacterial, bacterial-viral interactions in the nasopharynx and middle ear of young children with respiratory tract infection.