Alexander J. Travis, VMD, PhD
Associate Professor of Reproductive Biology
Laboratory of Reproductive Biology
Our lab has a broad range of interests and projects. We follow a philosophy of doing the best possible science while always keeping our eyes open for new opportunities to translate our work into improvements in the health of individuals or populations. Following these principles, our basic research in reproductive biology has taken us into new directions such as nanotechnology and medical diagnostics. A passion for wildlife conservation drives much of our work in animal reproduction, and is extending us in the other direction, working on the interface of biodiversity conservation and human poverty and hunger.
Our lab is a real team; we try to foster a high-energy, hard-working, supportive and highly collaborative environment. We like to have a mix of post-doctoral and research associates, graduate, veterinary and undergraduate students, and technical staff all working together. We strongly encourage creativity and new ideas, whether in basic science investigations or translation and entrepreneurship. Trainees from our lab have gone on to faculty positions running their own labs, highly competitive post-doctoral fellowships, and positions in government.
This web page describes several of our biomedical research projects. For more information on our wildlife projects, please visit our page at the Cornell Center for Wildlife Conservation.
A major new area of study in nanobiotechnology is being supported by an NIH Pioneer Award. These studies derived from work investigating the compartmentalization of metabolic pathways in sperm. We and others discovered that the enzymes of glycolysis are tethered along a cytoskeletal element in the principal piece of the sperm flagellum. This “solid state design” gives the sperm the ability to produce energy locally down the length of the tail—a critical adaptation in cells that have a highly restricted localization of mitochondria. We are employing a biomimetic strategy (copying a design from nature) to target these enzymes on hybrid organic-inorganic devices where they would function to produce energy in the form of ATP. If we can successfully build this whole pathway, it would enable the development of self-powered, implantable nanoscale medical devices, which could use circulating glucose as fuel. Such devices could carry out a variety of medical functions, such as delivering drugs to specific sites at defined kinetic rates over time. Now that we have many of the enzymes working while tethered, we are exploring other uses for them, such as point-of-care diagnostics to detect disease biomarkers, such as those for stroke. The use of these tethered enzymes has many advantages in speed, cost, and sensitivity in comparison to antibody-based biomarker detection.
The concept of pathway compartmentalization extends into signaling in our investigations of specialized membrane domains known as “membrane rafts.” These dynamic regions are highly enriched in sterols and sphingolipids, as opposed to phospholipids. Rafts are uniquely important to the processes through which sperm mature in the epididymis and in the female tract, as they acquire the ability to fertilize. We identified micron-scale segregations of sterols and the ganglioside GM1 in the sperm plasma membrane, as well as 3 distinct and highly reproducible sub-types of nanometer-scale rafts. Quantitative and shotgun proteomics and lipid biochemistry have defined these sub-types and identified targets for our current functional investigations. In particular, we are studying how sterol efflux enables sperm to fertilize, and how the lipid GM1 controls the process of acrosome exocytosis by regulating transient calcium fluxes that enable membrane fusion. Applications extend into technologies of assisted reproduction as well as cryopreservation and diagnosis of male fertility. Our assay of sperm function that diagnoses male fertility is currently being tested in a human clinical trial.
Development of new technologies of assisted reproduction are an important component of our work in wildlife and domestic animals that can serve as models for wild species. Although dogs are the most commonly seen animals in veterinary practices, very little is known about reproduction in dogs because they differ so much from other mammals. Their eggs are ovulated at a much earlier stage of development; they only cycle once or twice a year; and their hormone profiles are almost identical whether pregnant or not-pregnant. All these differences have resulted in almost no advancements in assisted reproduction. We don’t know how they come out of anestrus, so there are no optimized protocols to induce or synchronize estrus. We don’t know how to mature their eggs in the lab, so no puppies have ever been produced by in vitro fertilization. Lastly, the high lipid content of dog eggs has made freezing eggs or embryos very difficult. In collaboration with the Smithsonian Conservation Biology Institute, we are working on in vitro fertilization in the dog, maturing canine ooctyes, and cryopreserving canine embryos. Work on assisted reproduction in dogs can not only advance the veterinary care of pet and working dogs, but also be used as a foundation for studies of the reproduction of wild canids, such as African wild dogs or maned wolves.
We are also performing research and developing technologies based on spermatogonial stem cells. These cells are present from birth in the testes, whereas sperm are only produced after puberty. They therefore offer a way to save an animal’s reproductive potential even if it dies before producing sperm and reproducing. Unfortunately, this can be an important problem when populations of endangered species reach low numbers and there is any neonatal or juvenile mortality. Our work on testis xenografting is described here. We were also the first lab in the world to achieve succesful spermatogonial stem cell transplantation in the dog. This method is now being used in attempts to develop transgenesis in this species, which shares approximately 400 diseases with humans. These efforts will advance both human and veterinary medicine.
Link to The Doctor's Channel web interview with Dr. Travis on Spermatagonia Stem Cell Transplant, August 2008.