Ten-year anniversary: Ten defining discoveries and research collaborations in the School of Medicine Basic Sciences

In honor of the 10-year anniversary of the School of Medicine Basic Sciences, we are highlighting 10 incredible research achievements and research collaborations that have occurred since our inception in April 2016.

Follow along as we share more 10-item lists to celebrate our 10th anniversary throughout the months of April and May.

1. Expanding the SOMBS clinical trials pipeline: A defining milestone for the SOMBS came in November 2016, when the U.S. Food and Drug Administration approved an Investigational New Drug application for VU319, a drug for memory loss in people with Alzheimer’s disease and schizophrenia. This IND marked the first time a drug candidate owned by Vanderbilt University advanced to human clinical testing. Developed within the Vanderbilt Center for Neuroscience Drug Discovery (now the Warren Center for Neuroscience Drug Discovery), VU319 targets cognitive enhancement in Alzheimer’s disease and progressed to a phase I clinical trial. This achievement was made possible in part by the structural independence created through the Vanderbilt–VUMC split, which enabled more agile clinical translation.
   Since then, the program has built significant momentum, with multiple additional therapeutic candidates advancing toward or entering human clinical testing. Early-stage phase 2 trials are now underway or imminent, reflecting a growing pipeline of translational research.

   Beyond neuroscience, collaborations between SOMBS researchers and external partners have also driven oncology breakthroughs into clinical evaluation, including through a partnership between the laboratory of Stephen Fesik, the Orrin H. Ingram, II Professor of Cancer Research, and Boehringer Ingelheim that advanced a novel pan-RAS inhibitor.These recent advancements in therapeutic candidates underscore the SOMBS’s expanding impact on human health.

   

2. Pioneering a new class of antibiotics: As antibiotic resistance rises globally, the need for new therapeutic strategies has become increasingly urgent. To that effect, Neil Osheroff, the John Coniglio Professor of Biochemistry, recently played a central role in advancing one of the most promising breakthroughs in this space: the development of a new class of antibiotics. Building on decades of fundamental research, his lab helped launch the first novel antibiotic class in decades, an antibiotic that is now approved for the treatment of uncomplicated urinary tract infections and uncomplicated gonorrhea. 

   By showing how the drug, gepotidacin, targets bacterial topoisomerases (enzymes essential for DNA replication and cell survival), Osheroff’s research helped open a new pathway for combating pathogens that have become resistant to existing treatments. These efforts highlight the power of basic science to drive translational impact, bridging molecular mechanisms with real-world clinical applications. The resulting therapy represents a significant step forward in addressing antimicrobial resistance and underscores the SOMBS’s leadership in tackling some of the most pressing challenges in global health.

3. Mapping the dynamic structural of the bacterial flagellar motor and becoming a global science story: In a breakthrough that transformed how scientists visualize life at the molecular level, the lab of Tina Iverson, Alan D. Bass Professor of Pharmacology, revealed that the bacterial flagellar motor is not a static structure, but a dynamic, highly complex engine.

   Using advanced cryo-electron microscopy, the team captured near-atomic snapshots of the motor in multiple states and reconstructed how it rotates and switches direction, offering unprecedented insight into one of nature’s most sophisticated molecular machines. This rotary motor powers bacterial movement, enabling cells to navigate their environment through a process known as chemotaxis, which is central to infection and survival. By revealing how structural components shift to drive clockwise and counterclockwise motion, their work helps answer longstanding questions about how bacteria move and how that movement might be disrupted therapeutically.

    

   The impact has extended far beyond the lab. A widely viewed YouTube video by Destin Sandler of Smarter Every Day brought this molecular “movie” to a global audience, amassing millions of views and showcasing the power of basic science to inspire.

   Together, the discovery exemplifies SOMBS’s strength in combining cutting-edge technology, collaboration, and storytelling to illuminate the hidden mechanics of life.

   

4. Defining the structure and function of the AMPA receptor in a rare solo breakthrough in Science: In an extraordinary scientific achievement, Dr. Teru Nakagawa authored a single-investigator paper in Science detailing the structure and function of the AMPA receptor, one of the brain’s most essential molecular components and one that plays a central role in synaptic plasticity, learning, and memory. 

   Single-authored publications at this level are exceptionally rare, underscoring both the technical difficulty and intellectual leadership behind the work. Not only did Nakagawa reveal how these receptors assemble with auxiliary proteins and how their structure governs ion channel behavior and signaling, but this work provided key insights into how neuronal signals are transmitted and regulated at the molecular level. This feat stands as a powerful example of how deep expertise and innovative methodology can converge in a single-author effort to reshape an entire field.

5. Accelerating transformative biomedical research through TIPs awards: The Vanderbilt University Office of the Provost Trans-Institutional Programs Awards launched in 2015 as a $50 million initiative over five years to support cutting-edge research. By supporting emerging centers and reinvesting in established ones, TIPs enabled faculty from across Vanderbilt and Vanderbilt Health to tackle complex scientific challenges and position the institution as a leader in discovery.

   Several SOMBS-led TIPs projects exemplify this impact. TIPs helped Stevenson Professor of Biochemistry Kevin Schey establish state-of-the-art capabilities for analyzing metabolic signatures in the Mass Spectrometry Core, part of the Mass Spectrometry Research Center, to empower research across disease areas. TIPs also supported a reinvestment in the Center for Structural Biology by acquiring a new microscope, the Titan Krios, that enables the laboratory and its leading researchers, including Nakagawa and Iverson, to remain on the cutting-edge of structural biology research. The development of a novel nuclear magnetic resonance based in vitro diagnostic research platform was also developed thanks to TIPs. Advanced by Markus Voehler and collaborators, this investment in IVDr integrated sophisticated molecular profiling into both research and clinical applications.

   These initiatives highlight how TIPs funding catalyzed shared resources and interdisciplinary collaboration, amplifying the reach and impact of SOMBS discoveries across the biomedical sciences.

   

6. Bringing machine learning closer to fulfilling its drug development potential in a single-author Proceedings of the National Academy of Sciences paper: “Machine learning promised to bridge the gap between the accuracy of gold-standard, physics-based computational methods and the speed of simpler empirical scoring functions,” said Dr. Benjamin P. Brown, an assistant professor of pharmacology in the SOMBS. “Unfortunately, its potential has so far been unrealized because current ML methods can unpredictably fail when they encounter chemical structures that they were not exposed to during their training, which limits their usefulness for real-world drug discovery.”

   Brown was the sole author on a 2025 paper published in PNAS that is improving the way the field of drug discovery creates machine learning algorithms to predict a protein’s interactions with a small molecule. These improvements bring machine learning closer to fulfilling its potential in the field—something that has not been realized after more than a decade of work.

7. Defining the hallmarks of precancer: The hallmarks of cancer, a series of functional capabilities that human cells acquire as they transition from a normal state to a neoplastic state (a state of excessive and abnormal growth), have been used for over 25 years to guide researchers and clinicians as they seek to understand cancer.
   
   In 2024, Professor of Cell and Developmental Biology Ken Lau published an authoritative reference on the hallmarks of precancer. This seminal work lays out the principles that govern the biology of early, precancerous lesions, which are different from the principles that govern cancers. Lau’s work in this field has made him a celebrity in his field, and researchers have been known to approach him to take selfies with him during scientific conferences.

   

8. Launching a cadre of drug discovery startups: Our community members are all engaged in basic biomedical research, but the work they do can create paths toward new therapies or licensed applications. With the help of the Center for Technology Transfer and Commercialization, our community members can establish start-up companies and spinoffs to push their discoveries into translational applications. Since our school’s inception in 2016, the CTTC has aided in the establishment of nine start-up companies involving five faculty members.
   
   The newest spinoff, Septagen Pharmaceuticals, launched just this month with Heidi Hamm, professor of pharmacology, serving as its chief scientific officer. Septagen’s model seeks to use precision medicine approaches to reduce an unaddressed driver of cardiovascular health in women.
9. Rebranding dopamine as something beyond the “reward molecule”: For years, conventional wisdom indicated that dopamine was the reward molecule that fueled cravings for drugs and other substances by giving users hits of pleasure. Associate Professor of Pharmacology Erin Calipari changed how we view dopamine to more accurately acknowledge its role in learning from negative stimuli.
   
   “What my work has shown is that it’s not really a reward signal,” she said. “It responds to anything important in the environment, and it helps us learn. If you put your hand on a hot stove, that would also increase dopamine.”

   

10. Pushing discoveries through all our research programs: Science has always had “eureka” moments, but more often than not, it moves forward not in giant leaps, but in small, concerted steps forward. Our faculty, aided by their staff, students, and postdoctoral fellows, dedicate their daily lives to pushing the limits of what we know. This non-exhaustive list is but a sampling of the work that individual labs and their principal investigators have been doing over the first 10 years of the SOMBS:
    • An eye toward detail in DNA repair: The research program of David Cortez, the Hortense B. Ingram Professor of Cancer Research and chair of the Department of Biochemistry, includes such achievements as the discovery of the mechanism of replication fork reversal needed to deal with replication stress and thus maintain genome stability and the discovery of an entirely new mechanism of DNA damage repair that had not previously been described before.
    • A focus on cancers in the GI tract: A group of SOMBS and Vanderbilt Health researchers have been continuously funded by National Cancer Institute Specialized Programs of Research Excellence grants since 2002. The team, led by Professor of Medicine and Cell and Developmental Biology Dr. Robert Coffey, includes basic science faculty members and leaders, such as Ken Lau, and has been responsible for numerous discoveries throughout the years.
      Thanks to their latest grant

      , the Vanderbilt GI SPORE team—only one of four in the country—will soon launch a clinical trial to see if an investigational drug, when combined with the immunotherapy drug pembrolizumab, can overcome the resistance to immunotherapy intrinsic to the majority of colorectal cancer cases.

    • Making microscopic discoveries: Qiangjun Zhou, assistant professor of cell and developmental biology, seeks to answer fundamental questions in biology by bridging structural biology with cellular and molecular physiology. His lab uses structural biology techniques, including cellular cryo-electron tomography, to try to understand the molecular mechanisms of vesicle-mediated cell-to-cell communication in the central nervous system.
    • Redefining epigenetics: Emily Hodges, associate professor of biochemistry, focuses her lab’s work on epigenetics and epigenetic markers. Her re-examination of the role of DNA methylation (one type of epigenetic marker) in regulating transcription has challenged long-held beliefs in the field.
    • Utilizing biotechnological tools: AlphaFold is an artificial intelligence program developed designed to predict protein structures, and it has revolutionized the field of structural biology since it was first launched in 2018. In 2022, the labs of Hassane Mchaourab, the Louise B. McGavock Professor of Molecular Physiology and Biophysics, and Jens Meiler, Distinguished Research Professor of Chemistry and research professor of pharmacology, “hacked” AlphaFold2 and showed that it can also be used to study proteins that adopt multiple stable structural states as part of their function. Mchaourab is the leader of the Center for Applied AI in Protein Dynamics, which was established in 2023 to harness AI systems and machine learning technologies to advance the frontier of biomolecular dynamics, decipher the mechanisms of diseases, and improve human health.