Dr. Michaelle Chojnacki Awarded Two NIH Grants to Advance Innovative New Treatments for Tuberculosis
Dr. Michaelle Chojnacki
Saranac Lake, NY - Trudeau Institute is proud to announce that Dr. Michaelle Chojnacki has been awarded two competitive research grants from the National Institutes of Health (NIH) to develop groundbreaking therapies for Tuberculosis (TB) which is the leading cause of death globally by a pathogen, with 1.3 million deaths annually. While therapeutic interventions for Tuberculosis exist, they are lengthy, complex, accompanied by serious side effects, and can result in patient noncompliance. In addition to these public health issues, treatment is also complicated with increasing numbers of multidrug-resistant and extensively drug-resistant cases which result in high levels of treatment failures with significant mortality and limited treatment options. The development of new therapeutics for TB has been stagnant for over 40 years with many first line drugs dating back to the 1950s-1970s. In addition, many antibiotics target the same few bacterial pathways, where resistance mechanisms are already well established.
Dr. Chojnacki’s research laboratory at Trudeau Institute is dedicated to the discovery, development, characterization, and optimization of novel antimicrobial therapeutics for the treatment and sterilization of pathogens, including Mycobacterium tuberculosis (Mtb) and several other pathogens posing an immediate and increasing threat to human health. Dr. Chojnacki is committed to identifying novel drug targets and advancing chemically distinct compounds with unique mechanisms of action. Her team integrates expertise in bacterial pathogenesis, chemogenomics, and computational screening to rationally select and refine lead molecules that bypass known resistance mechanisms.
Both funded projects focus on bold, first-in-class strategies to combat drug-resistant Mtb, the bacterium that causes TB. The funding will allow her team and collaborators to accelerate the work on the discovery and optimization of small molecules that attack the pathogen in entirely new ways. That is an important step forward as antimicrobial resistance threatens current treatment options. “These awards recognize the urgency of the global TB crisis and the need for fundamentally new solutions,” said Dr. William Reiley, Director of Trudeau Institute. “Dr. Chojnacki’s work exemplifies the innovative science that defines Trudeau Institute.”
The NIH RO1 grant awarded to Dr. Chojnacki and her collaborators at Purdue University is a prestigious five-year NIH R01 grant that guarantees funding for Dr. Chojnacki’s lab for $2.8M over 5 years to advance a highly promising small molecule called TI-374 that shows strong activity against M. tuberculosis.
Preliminary data indicate that TI-374 acts on a previously unexploited bacterial target called alanine aminotransferase (AspC), an enzyme which has shown to be essential for bacterial survival of chronic TB infections. The drug compound had originally been developed for cognitive disorders and represents a promising drug repurposing opportunity that would significantly reduce development time, cost, and safety risks that are so common in the drug development process. Since this pathway has not yet been exploited by current TB drugs, the research project is seizing on an opportunity to establish a first-in-class therapeutic strategy that is designed to overcome the common resistance mechanisms pathogens have developed over time.
The proposal scored in the 7th percentile nationally, placing it among the top applications reviewed. The NIH R01 mechanism is widely regarded as the gold standard of independent research funding. Securing an R01 at this stage marks a significant milestone in Dr. Chojnacki’s career and highlights the national recognition of her innovative approach.
In addition to the R01, Dr. Chojnacki was also awarded a two-year NIH R21 grant to explore a second innovative therapeutic strategy. The R21 mechanism supports high-risk, high-reward research with strong potential for transformative impact.
This project focuses on the molecule TI-507, another small molecule identified using a computational chemo genomics platform. Unlike existing TB drugs, TI-507 is structurally distinct and shows activity against both actively growing bacteria and “persister” cells which are a dormant form of TB cells that are notoriously difficult to kill and contribute to prolonged treatment regimens.
Preliminary findings suggest that TI-507 disrupts NADP biosynthesis, an essential metabolic pathway in M. tuberculosis. The research will determine the precise molecular target of TI-507 and optimize the molecule for improved potency and selectivity. Furthermore, the research will focus on understanding whether the enzyme PpnK (NAD kinase) represents a new druggable TB target. By targeting bacterial survival mechanisms not addressed by current drugs, the project could help shorten TB treatment and improve outcomes for patients worldwide.
The $275,000 award is shared between Trudeau Institute and Virginia Tech, in collaboration with Dr. Webster Santos.
These awards build on Trudeau Institute’s historic leadership and reflect sustained federal investment in the Institute’s innovative drug discovery programs. Together, the two grants expand Trudeau’s pipeline of novel TB targets and reinforce its commitment to combating antimicrobial resistance, one of the most pressing and persistent global health challenges of our time. For Dr. Chojnacki, a rising leader in infectious disease research, the dual awards mark a major career milestone and position her laboratory at the forefront of next-generation TB drug discovery.
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Trudeau Institute, founded in 1884, is a not-for-profit biomedical research enterprise dedicated to immunology and infectious disease research, focusing on pathogens such as tuberculosis, influenza virus and the novel Coronavirus.