The Vanderbilt University School of Medicine Basic Sciences encompasses four departments: Biochemistry, Cell and Developmental Biology, Molecular Physiology and Biophysics, and Pharmacology. Through this article series, we are featuring each one, highlighting their proudest accomplishments, unique strengths, and visions for the future.
Medicines that Americans are taking today had their origin years, decades, or longer ago in basic research discoveries. The medicine our children and grandchildren will benefit from years from now are in turn being developed in basic science laboratories today.
There is one thing everyone should know about basic science, according to Ian Macara, chair of the Department of Cell and Developmental Biology at the Vanderbilt University School of Medicine Basic Sciences: everything you touch was developed by basic science, from food varieties and new crops to your phone, computer, and even the plastics we use every day. Not to mention, of course, everything in your medicine cabinet: prescription drugs, over-the-counter medications, drugs used in cancer clinics. Everything originally came out of a basic research lab.
Fundamentals of life
Macara, who is the Louise B. McGavock Professor of Cell and Developmental Biology, has been chair of his department since 2012 and is the sixth person to hold that position since its inception in 1925. The department’s mission is to advance basic biomedical research at the cellular, molecular, and organismal levels, and to train the next generation of scientists.
Cell biology is the study of cell structure, function, communication, differentiation, and division, and developmental biology is the study of tissue and organ formation and morphogenesis (how cells, tissues, or organisms develop their shapes). Together, they examine the principles of cell organization, function, and differentiation from stem cells into specialized cells, focusing on how they interact to form tissues, organs, and bodies.
Macara breaks it down even further. “You’re made up of about 37 trillion living cells of at least 1,000 different types, all of which come together to create your eyes, skin, brain, and the rest of you,” he said. “The cell is the fundamental unit of life, but it is unimaginably complicated.”
Why do cells die? Why do they live when they should die? Why don’t they die when they should? The researchers in his department want to understand it all.
Understanding how cells work is crucial for detecting diseases such as cancers, diabetes, and developmental disorders early (when they are most treatable) and for developing therapies against them. However, even a single cell is very complex, housing a variety of cell compartments, each with specialized functions. These organelles create a universe within a universe.
Strength through advancements
Vanderbilt’s CDB department is known for pushing the envelope in several key areas. For instance, Ken Lau, a professor renowned for his pioneering work on single-cell technology and the director of the Center for Computational Systems Biology, particularly within the context of colorectal cancer, recently challenged the long-held belief that cancers originate from a single mutated cell that proliferates. In a paper published in Nature just over a year ago, Lau and his collaborators revealed that multiple independently mutated cells may contribute to intestinal cancers—an amazing new concept in cancer biology.
“There is an interplay between cancer cells and their surrounding environment that we do not fully understand,” Lau said. “As a cancer progresses, it adopts its own complex evolutionary trajectory: each cancer cell or metastasis is like a different species, so there is no one-size-fits-all cure for cancer.”
Lau thinks we have a better chance of tackling the issue by focusing on the precancer stage. “Healthy people harbor many abnormal precancerous cells from which cancer may eventually develop, but if mutations are constantly occurring, why aren’t we full of tumors, and why does cancer mostly hit at old age? Those are the questions we try to answer,” Lau said. His goal is to find ways to identify these precancerous cells and leverage our understanding of them to stop them or periodically eliminate them.
Another research area within the department that is significantly impacting its field involves a technique that allows researchers to determine the location of various molecules to understand their spatial relationships. Jeff Spraggins, an associate professor in the department, leads a robust program that uses imaging mass spectrometry to molecularly analyze and localize metabolites, lipids, glycans, and proteins in tissues at a single-cell level in a variety of conditions, including kidney disease, infection, cancer, and others. In cancer research, IMS can be used to identify biomarkers, study tumors, and map drug distribution within tumor tissues. It also helps researchers understand how drugs are absorbed, distributed, metabolized, and excreted within the human body.
“The idea of developing technologies that can bring disease into focus has always been inspiring to me,” Spraggins said. “Imaging mass spectrometry and multimodal molecular imaging technologies have the potential to be a toolbox for precision medicine.”
In collaboration with Raf Van de Plas, who has an adjunct assistant professor appointment in the Department of Biochemistry at Vanderbilt but who’s primary appointment is as an associate professor Delft University of Technology in The Netherlands, the Spraggins lab recently created a high-resolution molecular atlas of the human kidney. Such a map, Spraggins said, might help doctors diagnose conditions earlier, tailor treatments to individual patients, or monitor responses at a molecular level.
Lau and Spraggins are co-leaders of a National Cancer Institute project aimed at developing a three-dimensional, multimodal molecular atlas of colorectal cancer at various ages after disease onset. This five-year initiative will establish the Vanderbilt Human Tumor Atlas Network center, which will be closely connected to the national Human Tumor Atlas Network, part of the NCI-funded Cancer Moonshot initiative.
A recent addition to the department, Qiangjun “QJ” Zhou has already made groundbreaking discoveries. In collaboration with Eric Skaar, professor of pathology, microbiology and immunology, Zhou described for the first time a structure inside pathogenic bacteria that captures iron, which is essential for bacterial growth. Bacteria are not typically thought to have any membrane-bound structures inside them, so the discovery of this novel structure, which they called a ferrosome, represents a breakthrough and a change to the paradigm.
In addition to his work on bacteria, Zhou is pioneering new methods in cryo-electron tomography, a powerful technique that allows scientists to see the three-dimensional structure of biological samples at high resolution while preserving the sample in a near-native state. Zhou is developing an innovative protein tagging technique that will allow for the visualization of specific proteins within cells—a significant advancement in cell biology. The technique, though still in development, promises to enhance our understanding of cellular structures by accurately tracking protein locations.
Investing in basic science today is the foundation for the cures of tomorrow
These breakthroughs offer a glimpse into the future where Department of Cell and Developmental Biology basic science lays the groundwork for innovations that can dramatically enhance human quality of life and understanding of complex biological systems.
“For thousands of years nobody had any clue what caused diseases,” Macara said. “It’s only been 140 years since we figured out that there are microbes, which cause health disorders, and look at people’s life expectancy now. The only reason most people in the United States are alive or enjoy extended, productive lives beyond age of 60 is because of basic science research.”
The journey to fully understand mechanisms of disease remains a daunting challenge, but every breakthrough moves researchers closer to finding answers. The Department of Cell and Developmental Biology is making great strides in unraveling the complexities of disease development at the cellular level and paving the way toward effective treatments and cures.