Bulitta Research Lab

Combating bacterial ‘superbugs’ via latest experimental and computational approaches

Bacterial ‘superbugs’ which are resistant to most or all antibiotics present one of the three most serious threats to human health in the US and worldwide. This has been highlighted by the World Health Organization, the US President’s Office, the European Union, and numerous national and international organizations. If bacterial resistance to antibiotics is not tackled successfully, a tremendous financial loss (>$1 trillion till 2050), widespread human suffering and an increased mortality from bacterial infections have all been predicted. Without effective antibiotic therapy, care of premature neonates, transplants, cancer chemotherapy and many other achievements of modern medicine will no longer be possible without significant risk. Therefore, society is on a path of reverting back to the pre-antibiotic era.

To combat this substantial global health crisis, the dynamic antimicrobial research team at Lake Nona is developing innovative antibiotic combination therapies which can successfully treat infections by these ‘superbugs’. This team is headed by Dr. Jürgen Bulitta who is an internationally recognized expert in antimicrobial pharmacology, latest in vitro infection models, and translational mechanistic modeling. His team is greatly enhanced by multiple fruitful collaborations with the UF Institute for Therapeutic Innovation located in the same building at Lake Nona, as well as a strategic network of national and international collaborators.

Dr. Bulitta has a long-standing interest in beta-lactam antibiotics which are the largest and most commonly used group of antibiotics. These drugs can be used safely in patients of all ages. However, there are substantial gaps in our understanding of how beta-lactam antibiotics can be used optimally which give rise to innovation combination therapies to combat ‘superbugs.’ This particularly applies to the use of two beta-lactams simultaneously. Such combinations can inactivate an optimal set of different target receptors (i.e. different penicillin-binding proteins, PBPs). Additionally, our team is developing novel approaches of how to enhance the penetration of antibiotics to their bacterial target sites. This research involves the development of innovative combination therapies which include beta-lactam, aminoglycoside, polymyxin and other antibiotics, as well as a beta-lactamase inhibitor.

The second research stream by Dr. Bulitta’s group focuses on human pharmacokinetics, pharmacodynamics and toxicodynamics. This includes advanced models of oral and inhaled drug absorption and greatly benefits from Dr. Yuanyuan Jiao’s expertise in clinical pharmacy. The latter research includes a fruitful collaboration with Dr. Guenther Hochhaus (COP, UF) in a stream of FDA-funded clinical studies. The latter assess important properties of inhaled corticosteroid formulations. This research is highly important for the development of the much-needed generic formulations for inhaled drugs.

Dr. Bulitta is continuously developing a free, open-source facilitator tool (SADAPT-TRAN) which greatly supports Quantitative and Systems Pharmacology (QSP) modeling in the S-ADAPT software package. This tool greatly enhances the capabilities and efficiency of researchers worldwide to perform translational, mechanistic modeling and optimally dose patients. These approaches and concepts are taught in Dr. Bulitta’s new course on “Translational Clinical Pharmacology” (PHA6133).

Ongoing Projects

Translational Antimicrobial Pharmacology

NIH/NIAID R01 AI136803 Bulitta JB (PI) Role: PI
Combating resistant superbugs by understanding the molecular determinants of target site penetration and binding

NIH/NIAID R01 AI130185 Bulitta JB (PI) Role: PI
Next-generation combination dosing strategies to combat resistant Acinetobacter baumannii

NIH/NIAID R01 AI148560 Tsuji BT (contact) / Bulitta JB  Role: PI
Novel Strategies for Antibiotic Combinations to Combat Gram-negative Superbugs

FDA HHSF223201710199C Luna BM (PI) Role: Subaward-PI
A Preclinical Mouse Model of Acinetobacter baumannii Infection For Antibacterial Development

Inhaled Corticosteroids

FDA U01 FD004943 Hochhaus G (PI) Role: Co-PI
Comprehensive Evaluation of Formulation Effects on Metered Dose Inhaler Performance, Food and Drug Administration

FDA HHSF223201310220C Hochhaus G / Bulitta J (PD/PI) Role: PD/PI
Study to investigate the sensitivity of pharmacokinetics in detecting differences in physicochemical properties of the active in suspension nasal products for local action

FDA 75F40119C10154 Hochhaus G (PI) Role: Co-PI
Systematic Evaluation of the Ex-Throat Plume Properties of MDI Formulations

Completed Projects

NIH/NIAID HHSN2722017000201 Miesel L (PI) Role: Subaward-PI
New Strain Testing and PK-PD Studies for Therapeutics in Murine Models of Bacterial Thigh Infections

NIH/NIAID R01 AI111990 Tsuji B / Li J (PD/PI) Role: Co-I
Novel PK/PD Strategies for Polymyxin Combinations against Gram-negative Superbugs

FDA HHSF223201610099C Bulitta JB (PI) Role: PI
Pharmacokinetic Comparison of Locally Acting Orally Inhaled Drug Products

State of Florida 7ZK30 Brown AN (PI) Role: Co-I
Identification of antiviral therapies for the treatment of Zika virus using existing drugs

NHMRC APP1101553 Project Landersdorfer CB (PI) Role: Co-I
Targeting hypermutable ‘superbugs’ in chronic respiratory infections by optimised antibiotic combination dosage regimens

 

Current Members

Jurgen Bulitta, Ph.D.

Antimicrobial Pharmacology, Chemistry; Professor of Pharmacotherapy and Translational Research; Preeminence Position

Bulitta,Jurgen

Yuanyuan Jiao, Ph.D.

Clinical Pharmacist, QSP Modelling Research Assistant Professor

Yuanyuan Jiao

Nirav Shah, Ph.D.

Advanced Imaging Postdoctoral Research Associate

Nirav Shah

Alaa Ropy Sayed, Ph.D.

Molecular Biology Postdoctoral Research Associate

Alaa Ropy Sayed

Yinzhi Lang, Ph.D.

Bioanalytics, Mass Spec., Glycoproteomics Postdoctoral Research Associate

Yinzhi Lang

Stefanie Drescher

Ph.D. Student Pharmacist, QSP Modelling Inhaled corticosteroids with Dr. Hochhaus

Stefanie Drescher

Elena Shin, M.Sc.

Pharmaceutics, Pharmacokinetics Ph.D. Student

Elena Shin

Carolin Werkman, R.Ph.

Pharmacotherapy Ph.D. Student

Carolin Werkman

Jieqiang Zhou, B.Sc.

Bioanalytics, Proteomics, Metabolomics Senior Bio-analyst and PhD Candidate

Jieqiang Zhou

Keisha Cadet, B.Sc.

Microbiology, Biotech, PK/PD Research Technician

Keisha Cadet

Rossie Jimenez, A.S.

Biotechnology, PK/PD Research Technician

Rossie Jimenez

Ann Ross Wlodarski, MHA

Research Coordinator

Ann Ross Wlodarski

Past Members

Bartolomé Moyá Cañellas, Ph.D.

Assistant Professor Fundació Institut d’Investigació Sanitària Illes Balears – IdISBa, Spain

Bartolome Moya

Tae Hwan Kim, Ph.D.

Assistant Professor College of Pharmacy Daegu Catholic University, Korea

Tae Hwan Kim

Mong-Jen Chen, Ph.D.

Senior Scientist Clinical Pharmacology AbbVie, Chicago USA

Mong Jen Chen

Hongmei Xu, Ph.D.

Sr. Director Clinical Pharmacology Karyopharm, Boston USA

HongMei Xu

Rajbharan Yadav, Ph.D.

Scientist Translational PK/PD Genentech Inc., San Francisco USA

Raj

Xun Tao, Ph.D.

Scientist Translational PK/PD Genentech Inc., San Francisco USA

Xun Tao

Dhruvitkumar S. Sutaria, Ph.D.

Associate Scientist Genentech Inc., San Francisco USA

Dhruvit Sutaria

Graduates Ph.D. Students and Former Co-Mentors

Graduates ph.D. Students Former Co-mentors
Dr. Neang Sok Ly Mr.Johannes Gareis
Dr. Soon-Ee Cheah Mr. Sven Huttner
Dr. Vanessa Rees Mr. Timothy Armstrong
Dr. Gemma Ryan Ms. Verena Jakob
Dr. Lisa Black Mr. Michael Rodamer
Dr. Tasnuva Tamanna

Past Interns and Assistants

Former Pharm.D. Research Interns Former Research Interns Former Research Assistants / Technicians
Mr. Andrew Zhao-Hui Li Mr. Markus T. Meyer Ms. Rebecca E. D’Hondt
Ms. Nurhayati Ahmad Noorzi Ms. Yuling Huang Ms. Holland DeFiglio
Ms. Bonnie Fung Ms. Phyllis Phua Ms. Jessica Shan
Ms. Cecilia Xu Ms. Nicolin A. Wanigaratne Ms. Yen Mei Chuah
Mr. Chanh Tin Michael Nguyen Mr. Gordon Shing Yip Lee Ms. Kate Rogers
Mr. Tuck Wong Ms. Emelie Olsson Ms. Lina Ly
Ms. Sally Hoang Ms. Annette Dahlberg Ms. Preeti Yadav
Ms. Lina Ly Ms. Neang Sok Ly Ms. Lijie Zhang
Ms. Sin Loo Wang Ms. Louisa K. M. Schlaak
Ms. Yi-Chu (Emelie) Wang Ms. Kirsten Prince
Ms. Jinq Ru Lim Mr. Alex Duarte
Ms. Yen Mei Chuah Mr. Benedikt C. Huck
Mr. Dung Ngo Mr. Nils Krumm
Mr. Nrec Dedaj Ms. Madeline Behr
Ms. Kristen Prince Mr. Kajetan Nierychlewski
Ms. Priscell Villegas Ms. Ann-Christin Pape
Mr. Brandon O Klee