The University of Pittsburgh Training Program in Antimicrobial Resistance
The University of Pittsburgh Training Program in Antimicrobial Resistance (Pitt TPAR), is an NIH-funded T32 multidisciplinary training program for pre-doctoral and post-doctoral trainees. The program focuses on translational science with the goal of having our trainees transition to postdoctoral fellowships or independent research careers. The overall goal of this T32 is to produce the next generation of scientists with the training, creativity, and resources to be future leaders in the critical field of antimicrobial resistance.
- Our philosophy is that trainees should be exposed to a broad spectrum of advanced, cutting edge, and novel approaches used in antimicrobial research to best prepare them to become creative and independent investigators.
- The overall objective of the Pitt TPAR is to provide a collaborative, interdisciplinary, and coordinated team-mentoring effort to trainees from diverse academic backgrounds to foster highly-skilled, independent investigators who have the technical, intellectual and leadership skills that will prepare them to make major contributions to the antimicrobial resistance field.
- This is accomplished through a co-mentorship structure, with one mentor being a strong content expert in the proposed area of research and the other(s) to be drawn from a range of disciplines as determined by the area of study. As illustrated in Fig.1, a key feature is the multidisciplinary approach, with the rationale being that novel antimicrobial resistance research is optimal when multiple tools and strategies are used: (i) basic research in pathogenesis and molecular mechanisms of resistance is important to develop novel diagnostic and therapeutic approaches; (ii) microbial genomics can be used to understand transmission and spread of drug-resistant pathogens, and to identify and track genetic elements that encode for resistance; (iii) research into the human microbiome provides information about how the microbiome influences transmission of and susceptibility to drug-resistant pathogens; (iv) bioinformatics is essential for analysis of big data sets from microbial genomic and microbiome studies and is an integral part of the work that is performed in the labs of many of our mentors; (v) epidemiology and biostatistical methods are used to study transmission and identify modifiable risk factors for drug-resistant infections and are also crucial for design of clinical trials; and (vi) infectious diseases modeling and simulation are used to leverage existing data by predicting transmission of drug-resistant pathogens, as well as estimating the impact of interventions.
- Unparalleled infrastructure and resources within the University of Pittsburgh and the University of Pittsburgh Medical Center (UPMC) creates a rich training environment for the Pitt TPAR.
- The Pitt TPAR encompasses an interactive and multidisciplinary environment where breakthroughs in basic sciences inform clinical practice, or ongoing and new, clinically important questions can be investigated in a laboratory setting. Our program draws faculty and trainees from diverse environments and creates a single “umbrella program” that integrates different disciplines and approaches to studying antimicrobial resistance. The Pitt TPAR is not a silo in a single department or graduate program. Importantly, the flow of ideas from researchers in different disciplines benefits both the trainees and training faculty.
- UPMC is the clinical and translational centerpiece of our training program (Fig.2). The institution is internationally recognized for pioneering research in solid organ transplantation, critical care medicine, high-risk gastrointestinal surgery, trauma medicine and HIV. UPMC is at the frontline in the battle against drug-resistant and other difficult-to-treat microbes. On average, 477 patients per year are diagnosed with C. difficile infection, 256 with carbapenem resistant Enterobacteriaceae, 228 with extensively-drug-resistant Pseudomonas aeruginosa, and 59 with multidrug-resistant Acinetobacter. Thirty-six percent of Enterococcus and 43% of clinical S. aureus isolates recovered at UPMC are resistant to vancomycin (VRE) and methicillin (MRSA), respectively. VRE and MRSA bacteremia occurs in an average of 72 and 101 patients per year, respectively. Candida bloodstream infections, Candida intra-abdominal infections, and invasive Aspergillus infections are each diagnosed in over 100 patients per year. As described below, clinical care and research programs have been developed in collaboration with UPMC to control and reduce each of these drug resistance challenges. The Pittsburgh AIDS Treatment Center, a dedicated HIV Primary Care Unit at UPMC, provides comprehensive medical care to over 1,000 HIV-infected men and women, over 20% who are enrolled in research studies sponsored by the NIH and industry. As such, the Pitt TPAR is uniquely situated in an epicenter of antimicrobial resistance and has access to high-risk patient populations, along with the associated electronic medical record data and rich repositories of drug-resistant isolates.
Epidemiology, molecular epidemiology, microbial genomics and the human microbiome
- Lee H. Harrison, MD can provide training on clinical and epidemiologic studies of drug resistance and the use of microbial genomic epidemiology in the study of emergence and transmission of drug-resistant bacterial pathogens.
- Vaughn S. Cooper, PhD can provide training in pathogen evolution, genomics, and bioinformatics.
- Alison Morris, MD, MS can provide training in the application of microbiome data to antibiotic resistance.
- Daria van Tyne, PhD can provide training in the genomics of antimicrobial resistance.
Biostatistics and modeling
- Maria Brooks, PhD can provide co-mentoring in study design and data analysis.
- Mark S. Roberts, MD, MPP can provide mentorship in infectious diseases modelling and simulation.
Bacterial mechanisms of resistance and pathogenesis
- Jennifer Bomberger, PhD can provide training in mechanisms of biofilm development and antimicrobial resistance in respiratory pathogens.
- Berthony Deslouches, MD, PhD can provide training on how antimicrobial peptides (AMPs) interfere with host-pathogen interactions by selectively disrupting the bacterial cell wall in both gram-positive and –negative organisms.
- Yohei Doi, MD, PhD can provide training in the epidemiology and mechanisms of resistance of drug-resistant Gram-negative pathogens.
- JoAnne L. Flynn, PhD can provide training in the mechanisms of pathogenesis and drug resistance of tuberculosis.
- Graham F. Hatfull, PhD can provide training in the molecular mechanisms of mycobacterial resistance to antimicrobials.
- Anthony Richardson, PhD can provide training in bacterial physiology, pathogenesis and host metabolism in drug-resistant staphylococcal species.
Fungal mechanisms of resistance and pathogenesis
- Cornelius J. Clancy, MD can provide training in translational research on echinocandin-resistant Candida, carbapenem-resistant pneumoniae, and other extremely drug-resistant Enterobacteriaceae.
- Sarah L. Gaffen, PhD can provide training in the immunology of resistance to fungal infections.
HIV mechanisms of drug resistance and pathogenesis
- Zandrea Ambrose, PhD can provide training on the impact of drug resistance on therapies in vivo and mechanisms of novel drug resistance pathways.
- John W. Mellors, MD can provide training in the mechanisms, epidemiology, management and prevention of HIV-1 drug resistance.
- Charles R. Rinaldo, PhD can provide training in pathogenesis of HIV infection in both treated and untreated individuals in the MACS.
- Nicolas Sluis-Cremer, PhD can provide training in mechanisms of HIV antiretroviral drug resistance.
Milestones for Pitt TPAR Trainees
- Graduate Students
We anticipate that each graduate student trainee will:
- present their research findings at one national or international symposium each year;
- publish at least one but preferably two first-authored peer-reviewed publications;
- complete their graduate training in fewer than 6 years (as described above our program will not support students for more than 3 years); and (iv) advance to a prominent post-doctoral position in an academic, industrial or government institution.
- Physician Scientists
One of the major concerns of aspiring physician-scientists is the time pressure created by the increasingly complex and multidisciplinary nature of combining research with clinical responsibilities. In general, the research years of physician-scientists are continually interrupted by month-long periods of required clinical training, which often stalls research that requires daily attention and continually adds to the time pressure. In order to circumnavigate the clinical intrusions into research training, we have frontloaded the clinical training of our programs into a consolidated 12 month period, subsequently allowing up to 2-3 years (depending on the progress of the fellow) of largely uninterrupted research training.
Specific milestones for clinical fellows will be to:
- present their research findings at one or more national or international symposium;
- publish at least one but preferably two first-authored research-driven peer-reviewed publications;
- apply for an NIH career development award;
- transition to an academic faculty position.
- PhD or PharmD Post-Doctoral Fellows
We expect that PhD or PharmD fellows will have identified their research interests and mentorship team before appointment to the Pitt TPAR. The primary goal of the mentor and Training Committee will be to prepare these fellows for independent academic careers. Therefore, in the third year of their training they will be expected to submit a K award (e.g. K99/R00), and transition toward a new phase of their career.
Specific milestones for PhD or PharmD post-doctoral Fellows include:
- present their research findings at one or more national or international symposia;
- publish at least one but preferably two or more first-authored research-driven peer-reviewed publications;
- apply for an NIH career development award;
- transition to an academic faculty position.
Division of Infectious Diseases
Academic Administrative Office
818 Scaife Hall
3550 Terrace Street
Pittsburgh, PA 15261
Center for Care of Infectious Diseases
Falk Medical Building
3601 Fifth Avenue
Pittsburgh, PA 15213
Patient Appointments: 412-647-7228