Science Stars: CVM Researchers Discuss Their Passions and Projects
The Cornell University College of Veterinary Medicine (CVM) has always been home to pioneers and thought leaders. The scientific inquiry in the labs and offices of CVM researchers has helped push new cures for human and animal diseases and has unlocked foundational insights into basic biology. We had a chance to conduct our own inquiry into three faculty members who have been carrying on the CVM tradition of asking big questions and making insightful discoveries: Drs. Carolyn Adler, Pamela Chang and Sabine Mann, Ph.D. '16.
Dr. Carolyn Adler
Assistant Professor, Department of Molecular Medicine
Q What has been your career path leading up to Cornell?
A I am a pure laboratory scientist and fell in love with molecular biology after college while working in a lab at Harvard. Then, I got my Ph.D. at the University of California, San Francisco, in biochemistry, where I worked with Dr. Cori Bargmann on understanding nervous system development in the roundworm C. elegans [planarians]. For my postdoctoral training, I went to Dr. Alejandro Sánchez Alvarado’s lab at the University of Utah. I chose to join his lab because he is an amazing mentor and has been a pioneer in establishing planarians as a new animal model for studying regeneration.
Q What drew you to CVM?
A Working in an environment where the training naturally incorporates an understanding of the differences and similarities between animals is inspiring. The longer I’m here, I realize what a gift it is to work side by side with people who are so passionate about the planet, and all of the creatures that inhabit it, as well as their interactions. Also, CVM made it incredibly easy for me to establish an aquatics system in a dedicated room where I culture thousands of planarians. Having the lab in the same building as the animal hospital, which has excellent water quality and facilities maintenance, was very attractive. In addition, the interconnectedness with other parts of campus offers many opportunities for collaborations, teaching, and interactions with students.
Q What is your scientific focus?
A My research focuses on organ regeneration and stem cells. Adult stem cells are present in our bodies, but aside from the skin, blood and liver, they are rare and not very good at replacing or repairing organs after damage. My laboratory studies adult stem cells in flatworms called planarians. Planarians are invertebrates capable of regenerating all of their organs, and even entire new animals, from tiny fragments. They accomplish this amazing feat through the action of adult stem cells, which make up 20% of their bodies. We are investigating the underlying mechanisms that enable their ability to regrow entire animals.
Q What drew you into this scientific area?
A When I was considering what field of research to focus on as a postdoc, I was drawn to non-traditional model organisms — basically, animals that are not commonly used in the laboratory, like mice and fruit flies. These animals are difficult to study because there’s not a community or history of researchers who have already built an arsenal of tools for experiments. Instead, if you want to do an experiment, you have to create it yourself. Regeneration is a field of biology that was popular to study in the 1800s and early 1900s, but fell out of favor in the late twentieth century. I wanted to be part of a burgeoning community that was resurrecting fascinating animal models and applying molecular biology knowledge to old observations. Regeneration incorporates my love of animals and cell biology, plus improving our understanding of it has huge potential for regenerative medicine.
Q What past projects are you most proud of?
A I am most proud of a project led by my first graduate student Divya Shiroor, which we recently published in Current Biology. In her first weeks in the laboratory, Divya discovered that stem cells, which normally die immediately after radiation exposure, don’t die as readily if animals are injured. Through sheer determination, Divya has now uncovered a mechanism for this ability of stem cells to avoid certain death. The reason I am so proud of this work is that before she started doing these experiments, neither of us could have imagined where they would end up. It proves that teamwork, commitment and drive can really build something new and creative, and this is what science should be.
Q What current projects are you most excited about?
A I am most excited by a project that explores stem cell biology at the level of single cells. About 20% of the planarian body is made up of stem cells, and many labs, including ours, are trying to identify which of these stem cells are critical for regeneration, and how they detect what tissues need to be replaced.
Using a method that we developed to remove a single organ, we can study and how stem cells initiate regeneration. A graduate student in the lab, Kuang-Tse Wang, is applying cutting-edge genomics tools to analyze the landscape of stem cells before and after amputations and to pinpoint which cells are responsible for driving organ regeneration.
Q What impacts or applications do you hope to see your work have on the world?
A I hope that our work will identify the fundamental mechanisms that enable stem cells to respond to injuries and equip them to regenerate whole organs in adult animals. As our population ages, it is very important to improve our arsenal of treatments for various diseases like cancer, where prognosis can be negatively impacted by injuries, radiation and organ deterioration. The information gained from our research will inform future treatments to mitigate aggressive cancers and diseases of aging.
Q What questions are you looking to answer next?
A There are many unanswered questions about planarian stem cells. At heart, I am a cell biologist and want to understand how these special cells are able to regenerate such complex tissues. What receptors do they have on their surface? How do they sense the presence and absence of particular organs? How do they receive energy? These questions will occupy my thoughts for the next few years.
Q What’s something most people don’t know about you?
A On Sept. 11, 2001, I was at a meeting at the Howard Hughes Medical Institute just outside of Washington, D.C., with my Ph.D. advisor and about 100 other scientists. After the planes hit the towers and the Pentagon, we realized that the only way to get back to San Francisco would be to drive. We rented two cars for 10 people, bought the only map available (a coloring book of the United States), and hit the road. We didn’t stop until Denver, mostly because one of the drivers was Louis Reichardt, the first American to summit Mount Everest and K2. We made it back to California in 48 hours. I have refused to drive across the country ever since.
Q What’s the best part of being a scientist?
A The colleagues. As a researcher, I interact with curious, creative and fearless students and colleagues. Also, helping to launch careers of undergraduates, graduate students and postdoctoral fellows is a great privilege.
Q What’s the most challenging part of being a scientist?
A Uncertainty. Even when you believe that a project will turn out well, it takes a lot of persistence and luck to make it work. It can be really challenging to keep pushing on particular projects when you don’t know what you’ll find, or if it will turn out the way you anticipated. The problem is that when it does work out as you hoped, the gratification is completely addictive!
Q What are the benefits of working at CVM and Cornell?
A The breadth of the life science community at CVM and at Cornell offers countless opportunities for collaboration and learning. I have graduate students from three different fields in my lab, and they each bring special expertise to the lab, spanning veterinary medicine, genomics and biochemistry. I can’t think of another institution that offers these particular strengths. These students and opportunities at Cornell have pushed our research in exciting new directions.
Dr. Pamela Chang
Assistant Professor, Department of Microbiology and Immunology
Q What has been your career path leading up to Cornell?
A I completed my bachelor’s degree in chemistry (minor in biology) at the Massachusetts Institute of Technology and my Ph.D. in chemistry at the University of California, Berkeley. Afterwards, I pursued my postdoctoral studies at Yale University School of Medicine in immunology.
Q What drew you to CVM?
A CVM has great colleagues and the excellent students and scholars who come to study here. I was also drawn to the fantastic environment for basic science research and amazing facilities for animal model-based research.
Q What is your scientific focus?
A We apply our expertise in immunology, microbiology and chemical biology to understand metabolism of the gut microbiome and their production of small-molecule metabolites that affect host physiological processes and inflammatory diseases.
Q What drew you into this scientific area?
A I became interested in this area during my postdoctoral studies, which was during a time when the field of gut microbiome research was beginning to burgeon.
Q What past projects are you most proud of and why?
A When I was a graduate student, my work pushed the boundaries of click chemistry, which is now a widely used methodology for labeling proteins, carbohydrates and other biological molecules with imaging agents, among other applications. During my postdoctoral studies, I discovered that gut microbially-produced short-chain fatty acids inhibit the inflammatory activities of intestinal macrophages. Since then, many research groups have found that these metabolites regulate several different immune cell types and inflammatory diseases in both animal models and humans.
Q What current projects are you most excited about and why?
A I am excited about our work in characterizing new microbial metabolites that affect the host during inflammation and infectious diseases. Further, we build on these discoveries to develop precision chemical tools to understand the metabolic pathways that lead to the production of these metabolites. Both of these research areas are exciting because there is so much to discover and understand in these pathways.
Q What impacts or applications do you hope to see your work have on the world?
A My dream is that our discoveries will lead to prophylactics or therapeutics that could be used to prevent or treat inflammatory and infectious diseases.
Q What questions are you looking to answer next?
A We are eager to explore how other classes of metabolites and biosynthetic enzymes beyond the ones that we study might impact inflammatory and infectious diseases.
Q What’s something most people don’t know about you?
A I grew up in Huntsville, Alabama, where my coolest summer job was working at NASA for a high school internship. My biggest regret there was not going to space camp!
Q What’s the best part of being a scientist?
A The part that I enjoy the most is mentoring the students and postdocs in the laboratory and being able to share the excitement in our discoveries and breakthroughs in the lab.
Q What’s the most challenging part of being a scientist?
A The part I find most difficult is staying original. There is “group think” in science, so once you publish a finding or concept, many others will often follow suit, and therefore it’s a constant challenge to move into creative, unexplored areas.
Q What are the benefits of working at CVM and Cornell?
A Cornell CVM and the greater research community throughout the university are, collectively, a very collegial and friendly environment that is conducive for collaborations that drive our interdisciplinary research.
Sabine Mann, Ph.D. '16
Assistant Professor, Department of Population Medicine and Diagnostic Sciences
Q What has been your career path leading up to Cornell?
A I completed my degree at the University of Veterinary Medicine, Hannover in Germany in 2007. After graduation I came to Cornell for the first time to complete an internship and a year of residency in the ambulatory clinic. Although I left to complete my residency and bovine health management specialization back in Germany, the Cornell ties from my initial years here remained strong. It’s no wonder that I came back to start working on my Ph.D. in the Biomedical and Biological Sciences Program in 2012. I have been at Cornell ever since (first as a grad student, then as a postdoc) and returned to my ambulatory roots in 2017 with a clinical and research appointment as assistant professor.
Q What drew you to CVM?
A I came to Cornell initially in 2007 because of the excellent reputation of its large animal clinical services (both in-house and ambulatory) and because I could work on all large animal species that interest me. The books and papers that we studied in vet school often had a Cornell author on them, and I knew that I could learn a great deal by coming here. When I returned for my Ph.D., I was particularly attracted by the training in epidemiology that is offered here, and because there are numerous faculty at Cornell who are internationally recognized as leaders in the field of dairy herd health and have been instrumental in advancing our field of study for decades.
Q What is your scientific focus?
A My research focuses on the critical phases in the life of agriculturally important animals, such as dairy cattle, where nutrient supply, metabolism and immune response are particularly challenged and result in loss of host resilience and increased risk for disease. For example, this is the case in the dairy cow's transition period from pregnancy to lactation and in the adaptation of the neonate to extrauterine life.
My background is in metabolism and nutrition, but I am currently integrating nutrient-sensing and nutrient regulation of immune response as part of my research focus, and I have a particular interest in how nutrient deficit or abundance shape inflammation. I have also recently extended my research to consider colostrum production and quality as well as immunologically active factors in colostrum and transition milk, and how these shape the immune maturation of the neonate.
Q What drew you into this scientific area?
A The overarching goal of my research is to improve the health and well-being of the animals that we work with every day and that people's livelihoods rely on. Ruminants produce food (milk, meat) or fiber for us, and I also still work with many farms that use horses as work horses or as a means of transport. These animals deserve our care and continued scientific discovery to adapt to existing and new individual and herd health challenges.
When I think of who influenced me, it was probably my grandfather, born in 1926, who first instilled in me the respect for these animals and a fascination for nature. In his lifetime, the role of agriculturally important animals changed immensely, and society's appreciation for their products and work is different now than it was a century ago.
Q What past projects are you most proud of and why?
A I am proud of several projects that have culminated in targeting the mTOR pathway as one potential contributor to immune dysfunction in the postpartum period. This nutrient-pathway is well conserved between species and as a central regulator of metabolism and physiology was an obvious target that I chose for my lab to work on initially. However, when this work began, we knew little about the role of this pathway in bovine immune cells, although its role is well documented in humans and rodent models.
Through a series of experiments, my lab has shown that this pathway is involved in the innate immune response. Its pharmacological inhibition in vitro produces a phenotype in antigen-presenting cells that closely resembles the changes seen postpartum and that are thought to be associated with heightened inflammation. Dr. Anja Sipka, a research associate in my lab, joined this work early on and brought her expertise in bovine immunology. We secured funding through the USDA AFRI foundation program and she was instrumental in moving these exciting projects forward in my lab together with my technician Suzanne Klaessig.
Q What current projects are you most excited about and why?
A We have recently established an in vivo LPS challenge model in postpartum cows that produces a reliable and predictable inflammatory response. I am particularly excited about this work led by my postdoctoral associate Dr. Tawny Chandler as we were previously limited by the lack of an adequate model. We are now using this model to investigate the modulation of inflammation in response to altering the amino acid supply and other interventions with importance to the postpartum cow. Furthermore, we plan to use this model to investigate the effects of supplemental calcium during an inflammatory response. This project idea derives from the long-pondered question if we are harming or helping cows by treating them with calcium supplements during the postpartum period. I am excited about this branch of my research as we can move our findings in these studies rapidly into possible interventions in the field.
Another area of my research that will deliver results that are readily applicable in the field is a series of projects led by my Ph.D. student Trent Westhoff. He is investigating the management and diet factors that contribute to production of high-quality colostrum production by dairy cows. Due to the particularities of placentation in cattle, colostrum is fundamentally important for the immunologically naïve bovine neonates. In these projects we are interested in heat stress, other seasonal influences and diet (energy and protein availability) as potential factors that we can harness to improve colostrum volume and quality.
Q What impacts or applications do you hope to see your work have on the world?
A My hope is that my research contributes to improved health and well-being of agricultural animals and to the livelihood of their owners. And I hope that my clinical work and teaching will contribute to educating another generation of veterinarians and animal scientists to have their own impact.
Q What questions are you looking to answer next/areas you plan to explore?
A In addition to the postpartum period, the postnatal period is equally risky for cattle and a time where we see high disease risk and a dysfunctional immature immune system. I am currently exploring the role of non-immunoglobulin colostrum and transition milk components and their potential roles in immune maturation of the neonate. In addition, my lab is studying the influence of post-harvest interventions, such as heat-treatment or freezing of colostrum on these colostral components. A pilot study of my lab used proteomics and metabolomics approaches to generate hypotheses, which we are now planning to address in a series of follow-up studies.
Q What’s something most people don’t know about you?
A I worked as a volunteer in an Irish Peace and Reconciliation center in County Wicklow for six months before going to vet school, mostly learning how to cater for large groups of students and politicians that engaged in conversations about the Troubles and how to move forward from this conflict.
Q What’s the best part of being a scientist?
A The best part of being a clinician scientist is that we are continuously involved in a cycle of discovery and change. We can take challenges or questions that we encounter in our clinical work to frame hypotheses that need to be tested by our research. We can then work on them in a collaborative environment with our colleagues and students from different fields. Ultimately, this in turn informs our clinical decision making and management of animals to improve health, well-being and productivity.
Q What’s the most challenging part of being a scientist/doing research?
A Balancing the unpredictability of science and discovery with one's own expectations of progress.
Q What are the benefits of working at CVM? At Cornell?
A Cornell CVM has an excellent group of faculty in my specialty, many of whom I am proud to collaborate with. It is embedded in an agriculturally important and active area, which enables the direct exchange between our stakeholders and our research, and this helps us stay relevant. Cornell is able to attract outstanding students and other trainees who are fun to work with and who keep us on our toes! •