Leadership
Our Director
Dr. Thomas J. Walsh serves as the Founding Director of the Center for Innovative Therapeutics and Diagnostics (CITD) in Richmond, Virginia. After obtaining his M.D. at The Johns Hopkins University School of Medicine, Baltimore, MD, Dr. Walsh trained over 10 post-doctoral years in infectious diseases, antimicrobial pharmacology, medical mycology, host defenses, pathology, and oncology at Johns Hopkins University, University of Maryland, and the National Cancer Institute. He is board-certified in Medicine, Infectious Diseases, and Oncology. During his 23 years at the National Cancer Institute in Bethesda, MD, Dr. Walsh became the Chief of the Immunocompromised Host Section in the Pediatric Oncology Branch, where he directed a combined laboratory and clinical translational research program dedicated to the pharmacotherapeutics, immunopharmacology, and molecular detection of invasive fungal infections in pediatric and adult patients with cancer, hematopoietic stem cell transplantation, and HIV infection. Following nearly a quarter century of dedicated government service, Dr. Walsh was recruited to serve in 2010 as the Founding Director of the Weill Cornell/New York Presbyterian Hospital Transplantation-Oncology Infectious Diseases Program, which consisted of the Patient Care Service, Translational Research Laboratory, and Clinical Research Unit. Over 12 years, as Professor of Medicine, Pediatrics, Microbiology & Immunology, Dr. Walsh led the development of the Transplantation-Oncology Infectious Diseases Program, implemented leading edge translational research, introduced major educational and mentoring initiatives, and provided expert and compassionate patient care.
As the author of more than 1,100 publications and investigator for more than 100 clinical studies, he and his Program have laid the scientific foundation for major advances and standards of care in diagnosis, treatment, and prevention of invasive mycoses in immunocompromised pediatric and adult patients with cancer and stem cell transplantation. His translational research is responsible for elucidating the pharmacological properties of every major systemic antifungal agent currently used in pediatric and adult patients for life-threatening mycoses. In response to the global public health crisis of multidrug resistant Gram-negative bacterial infections, he and his staff expanded their clinical research and laboratory investigations to develop new antimicrobial therapeutic agents in novel model systems leading to clinical trials against these life-threatening diseases. In summary, Dr. Walsh’s translational research from laboratory to clinic trials to standards of care has greatly advanced the science and saved the lives of numerous immunocompromised patients worldwide.
Antifungal Pharmacology and Therapeutics
Within the field of antifungal pharmacology and experimental therapeutics, Dr. Walsh and his team have methodically investigated the pharmacology, experimental therapeutics, and clinical activity of all the major classes of antifungal agents (polyenes, lipid formulations, triazoles, and echinocandins), as well as numerous experimental classes.
Dr. Walsh was the first to organize a consortium of pediatric institutions to study the safety and pharmacokinetics of antifungal agents to provide the foundation for accurate dosing of these compounds against life-threatening invasive fungal diseases. Through his organizing abilities and vision, this consortium has systematically studied the pharmacokinetics of all of the major antifungal agents used to treat life-threatening infections in children during the past three decades: lipid formulations of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, micafungin, and anidulafungin. The result of this translational research has provided pediatricians worldwide with the knowledge of dosing in children and adolescents that will allow their dosages to provide comparable plasma exposure to those of adults and thus prevent under-dosing of antifungal agents in thousands of children.
Dr. Walsh and a consortium of his colleagues also have systematically investigated the pharmacokinetics of all systemic antifungal agents currently used in pediatric patients to provide the foundation for accurate dosing of these compounds against life-threatening invasive fungal diseases. During the past three decades, his Program has developed 27 rabbit models of invasive pulmonary, disseminated, CNS, esophageal, gastrointestinal, oropharyngeal and catheter-related infections that closely replicate the profoundly immunocompromised patients with neutropenia or stem cell transplant in our oncology/BMT population. The models of primary pulmonary aspergillosis, fusariosis, mucormycosis, scedosporiosis, Exserohilum rostratum meningitis, as well as disseminated and catheter related models of invasive candidiasis, and trichosporonosis are microbiologically, histologically, immunologically, and radiologically highly replicative of the conditions of which are encounter in patients. The antifungal activities in these novel model systems have laid the foundation for and have been predictive of the therapeutic outcome in numerous clinical trials, which in turn have revolutionized antifungal therapy over the past quarter century.
Molecular Biomarkers for Diagnosis and Therapeutic Response
Beginning with the first detailed description of the correlation between responses of galactomannan antigenemia to antifungal therapy in experimental invasive pulmonary aspergillosis in 1992, he and his co-workers have systematically characterized the in vitro and in vivo factors contributing to the expression circulating enolase, D-arabinitol, galactomannan, non-Aspergillus galactomannan, D-mannitol, (1®3)-b-D-glucans, glucuronoxylomannan, and molecular and circulating DNA with genes of the ItS-1, ITS-2, 5.8S, 18S, and 28s regions the rRNA operon, as well as new proteomic
markers. Proceeding from bench-to-bedside, he and his colleagues have studied these biomarkers in patients with invasive candidiasis, CNS Candida infections, pulmonary aspergillosis, and pulmonary mucormycosis. Further studies using the T2-Biosystem and Karius cell free metagenomic assays are further helping to identify invasive fungal infections earlier in the course of infection to allow for early targeted antifungal therapy.
Immunopharmacology and Host Defenses
Dr. Walsh’s Laboratory has laid important foundations in our understanding of the role of the immunopharmacology of cytokines, immune augmentation of innate host defense and their relation to antifungal chemotherapy. Working in collaboration with Dr. Emmanuel Roilides and colleagues from several laboratories, Dr. Walsh’s Program has elucidated and documented the functional biology of GCSF, GMCSF, MCSF, interferon-gamma, TNF-alpha, TGF-beta, IL-13, IL-10, IL-8, IL-4 and other molecules in augmenting, suppressing, or modulating host response innate host response of neutrophils polymorphonuclear leukocytes, monocytes, and pulmonary alveolar macrophages against Candida spp., Aspergillus spp., Mucorales, Fusarium spp., Scedosporium spp., and Exserohilum rostratum. They have characterized elements of the signal transduction pathways of these cytokines and have demonstrated the role of GMCSF and interferon–gamma in reversing corticosteroid induced immunosuppression of monocytes, macrophages, and neutrophils. Understanding the immune activation properties of these antifungal compounds has provided novel insight into their mechanisms of action.
Multidrug Resistant Bacterial Infections
Dr. Walsh and his team have responded robustly to the rapidly emerging public health threat of multidrug resistant (MDR) Gram- negative bacterial infections through laboratory investigation and clinical research to develop new antimicrobial therapeutic agents and strategies in novel model systems leading to clinical trials to combat these life-threatening diseases. Using highly predictive rabbit model systems of Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Klebsiella pneumoniae (KPC) pneumonia, we are investigating new antimicrobial agents in the battle against organisms. They are also harnessing the power of bacteriophages using the whole virus, as well as their purified lytic enzymes, to treat disseminated MDR infections in murine models and pneumonias in rabbit models. The data from these models are leading to new clinical protocols for treatment of these lethal infections in patients.
Translational Antimicrobial Development
Dr. Walsh and his team through their translational research efforts have contributed to the preclinical and clinical research of 19 antimicrobial agents from bench to bedside in pediatric and/or adult patients: amphotericin B, amphotericin B lipid complex, liposomal amphotericin B, flucytosine, caspofungin, micafungin, anidulafungin, fluconazole, itraconazole, voriconazole, posaconazole, ravuconazole, isavuconazole, ibrexafungerp, novobiocin/rifampin, trimethoprim/sulfamethoxazole, ceftazidime, ceftazidime/avibactam, and ceftolozane/tazobactam.
COVID-19
Since 2020 Dr. Walsh and his team responded robustly to the challenges of COVID-19. These responses included direct care of the most seriously ill hospitalized patients, particularly during the apogee of the pandemic in 2020. Clinical research protocols investigated by the Clinical Research Unit include the epidemiology, clinical manifestations, host defenses, molecular detection, and innovative therapeutics, which include remdesivir, monoclonal antibodies, convalescent plasma, host response, and a wide range of immunomodulators investigated through industry and NIH sponsored grants. Dr. Walsh also served on the Weill Cornell COVID-19 Clinical Research Task Force, which helped to guide implementation of clinical trials for treatment of COVID-19. Further work supported by the Hellenic/American Fellowship/Mentorship, AHEPA, and the Henry Schueler 41&9 Foundation has identified a new class of orally bioavailable small molecules (thiadiazoles and benzothiazoles) that are potent inhibitors of the SARS-CoV-2 main protease. Dr. Walsh and his team also served as educator resource of COVID-19 to numerous medical, institutional, industrial, and lay communities.
Teaching and Mentoring
Dr. Walsh’s dedicated mentoring and inspiring clinical teaching in Medical Mycology, Microbiology, Immunology, and Infectious Diseases have been recognized through numerous awards and student evaluations. During the past three decades, Dr. Walsh has taught Medical Mycology to more than 6,000 medical students and graduate students in his lecture series at Weill Cornell Medicine, Johns Hopkins University, and University of Maryland Schools of Medicine.
Dr. Walsh also has mentored more than 200 students, residents, fellows, microbiologists, medical mycologists, pharmacists, immunologists, nurses, technologists, and junior faculty from 39 different countries in the field of Medical Mycology and infectious disease. Many are now emerging or established leaders in the field of antimicrobial pharmacology, antifungal therapeutics, medical mycology, host defenses, and infectious diseases with particular focus on invasive fungal infections and multidrug resistant bacterial infections complicating cancer, pediatric malignancies, and immunodeficiencies, as Associate Professors or full Professors of Pediatrics, Medicine, and/or Microbiology and Immunology. Several have achieved important roles in the USPHS, NIH, and FDA. During the past decade, he has served as mentor or co-mentor on six K-23 and K-08 awards to University medical center junior faculty, all of whom have made stellar achievements in the fields of pediatric mycology or antimicrobial pharmacology, including Awards from the ASM, Children’s Oncology Group, and Pediatric infectious Diseases Society.
Organizational Leadership
Dr. Walsh has demonstrated outstanding leadership throughout his career in many related areas of Infectious Diseases. He has served as President and Councilor of the MMSA, Councilor of the International Immunocompromised Host Society, Chair and Councilor of the Medical Mycology Division of the ASM, and as President of the Medical Mycological Society of New York (MMSNY). He has organized and chaired numerous educational sessions at national and international meetings, chaired working groups within the NIAID MSG and BAMSG, served on editorial boards and as reviewer for numerous journals in infectious diseases and medical mycology, co-chaired the IDSA Guidelines Committees for Aspergillosis, served on multiple national and international grant review committees, organized the first two Henry Schueler Foundation International Forum on Mucormycosis, chaired the CPIC Guideline Committee on implementation of genotypic data guiding the use of voriconazole, and co-founded International Consortium for Study of Osteoarticular Mycoses with Institute Pasteur in France.
Clinical Resource and Direct Service to Patients
Dr. Walsh also serves as a key institutional, national, and international expert in the care of patients with invasive fungal diseases and opportunistic infections in immunocompromised patients. Dr. Walsh and his team in the Clinical Service of the Weill Cornell Medicine Transplantation-Oncology Infectious Diseases Program provided state of the art, advanced, and compassionate care to immunocompromised patients at NYPH. He has directly impacted on the lives of hundreds individual patients with life-threatening mycoses. Dr. Walsh also has provided his expertise in bringing the best advances from bench to bedside in the care of more than 1,000 pediatric and adult patients with life-threatening mycoses from more than 280 institutions in the United States and 86 institutions from 38 other countries. The physicians caring for these patients and their families often have said that many of these patients would not have survived if it were not for Dr. Walsh’s direct intervention: www.missionfromtheheart.org