Our Science

Keeling Center scientists are currently evaluating cross-sectional and longitudinal changes in immune function, neuroanatomy, biomarkers and cognition in multiple primate species as a means of characterizing individual and phylogenetic variation in aging. The goal of these studies is to identify similarities and differences in the process of aging on biological systems between species. Further, data generated from these efforts can be used to enhance subject selection by investigators based on specific biological, neurological or cognitive characteristics of interest.

With collaborators at the New York University School of Medicine, we are exploring the use of an adjuvant to induce a targeted immune response without producing excessive and sustained inflammation aimed at eliminating beta amyloid plaques from the brains of aged squirrel monkeys. Cerebral amyloid angiopathy (CAA) is one of the morphologic changes seen in the brains of Alzheimer’s disease patients that has been associated with dementia and intracranial hemorrhage. A protein, called beta amyloid, when deposited in and around the vessels in the brain, disrupts normal blood flow, particularly when associated with small blood vessels, capillaries. Squirrel monkeys naturally develop these amyloid plaques and can serve as a model for exploring therapies. Using a combination of memory tests and MRI scans, we hope to show effectiveness and safety of this novel immunomodulatory therapeutic approach.

Our research pioneered vaccine development against HIV. We are also developing a prime-boost vaccine delivered using bioengineered viral vectored and adjuvanted protein, for mucosal route as a needle-free, safer and more practical approach for global application. Another project is focused on targeting persistent HIV reservoirs and a nanochannel drug delivery system (nDS). The nanochannel delivery implant (NDI), a subcutaneously implantable device for sustained and constant delivery of anti-HV drugs such as tenofovir alafenamide (TAF) and emtricitabine (FTC). Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. 

In collaboration with experts in infectious diseases, virology and obstetrics, the Squirrel Monkey Breeding and Research Resource has begun several important studies of Zika virus in neotropical primates. More than seventy species of neotropical primates live in South and Central America and may serve as reservoirs for Zika virus in nature. The results of our ongoing studies of Zika virus infectivity and transmission in squirrel monkeys may have important implications for the control of Zika virus in nature and provide a novel animal model for testing of vaccines and antiviral medications to combat Zika virus in humans.

The Section of Primate Behavior and Environmental Enrichment of the Michale E. Keeling Center for Comparative Medicine and Research of The University of Texas MD Anderson Cancer Center is among the world’s leaders in primate behavioral management. Home to approximately 2500 nonhuman primates, including great apes, old world monkeys and new world monkeys that live socially in breeding and research colonies, our section is dedicated to maintaining and enhancing our primates’ well-being and welfare.

Combining a variety of socialization strategies, environment enrichment practices, and positive reinforcement training techniques that functionally simulate natural conditions, every primate is given multiple opportunities to express all activities that comprise their species-typical behavioral repertoires. Ranging from the simple provision of manipulable objects to the presentation of devices that stimulate natural foraging behaviors to the use of computerized touch screens that allow the primates to use their impressive cognitive abilities, the environmental enhancement plan at the Keeling Center provides multiple opportunities for the animals to prosper. Positive reinforcement training techniques allow the primates to voluntarily participate in a variety of research, husbandry and veterinary procedures, giving them many opportunities to make meaningful choices and to exert control over their environments.

Multiple postdoctoral, Ph.D., master’s and undergraduate students from local colleges, universities in the United States and universities in Denmark, the UK, Kenya and Indonesia have conducted behavioral research projects with the primates in our colonies. Historically, the behavioral management group at the Keeling Center has not only worked to enhance the welfare of the primates living in our colonies, we have also dedicated considerable effort to disseminating our successful behavioral management practices to those who manage primates at other facilities, including research laboratories, breeding colonies, contract research organizations, zoological parks, and sanctuaries.

We have organized a variety of educational conferences (Primate Behavioral Management Conference) and workshops (Primate Training and Enrichment Workshop) at the Keeling Center for more than 30 years. Almost 1000 individuals responsible for various aspects of primate care from well over 130 facilities that cumulatively house over 100,000 primates around the world have participated in our programs. Members of the section have also edited and authored chapters in the Handbook of Primate Behavioral Management (2017), Behavioral Biology of Laboratory Animals (2022), and the Handbook of Laboratory Animal Science (2022), all published by Taylor and Francis’ CRC Press. Maintaining and enhancing the welfare of the primates at the Keeling Center is an ongoing process, and we are constantly striving to take behavioral management to the next level. 

Colorectal cancer (CRC) is the third-leading cause of cancer deaths among humans worldwide and is the most common cancer of rhesus macaques. Rhesus macaques share 93% DNA homology with humans and naturally develop forms of CRC that closely mimic CRC in humans, specifically those characterized by microsatellite instability (MSI) resulting from defects in mismatch repair (MMR) genes. In humans, germline mutations of the MMR genes (MSH2, MSH6, MLH1 and PMS2) result in hereditary nonpolyposis CRC (HNPCC), also known as Lynch syndrome. In addition, non-hereditary defects in MMR genes can be acquired through “second-hit” somatic mutation, or through epigenetic changes such as abnormal methylation of promotor regions.

In our rhesus macaque breeding colony, in addition to spontaneous somatic mutations or methylation, we have identified unique germline mutations in MLH1 and MSH6 in animals with CRC, modeling Lynch syndrome. We are working with collaborators to characterize and develop the rhesus macaque model of Lynch syndrome and to develop therapies for prevention and treatment of CRC.

Figure: Microscopic image of a colon carcinoma in the proximal colon of a 23-year-old rhesus macaque. Invasive neoplastic intestinal glands are surrounded by fibrous stroma with few infiltrating inflammatory cells.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, a zoonotic vector-borne pathogen transmitted by triatomines, also known as kissing bugs. About 6 to 7 million people are infected worldwide, primarily in Latin America, but local transmission also occurs in the southern United States, especially among wildlife and dogs. Approximately 20–30% of infected individuals will develop disease later in life, including heart disease, cardiac arrest or enlarged colon. Current therapies are significantly limited and developing a safe and effective vaccine or drug therapy against T. cruzi is critically important.

With collaborators, we are studying natural T. cruzi infections in rhesus monkeys, which occur at a low incidence in our colony. Vector-borne transmission is the most important route, and we have not identified any evidence of direct transmission between animals. Our naturally infected rhesus monkeys are being used as models to test new therapeutics and have been critical to developing diagnostics to be used as a “test for cure” for drug development studies and clinical trials.