Michael P. Muehlenbein, PhD, MsPH

Featured Current Projects

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1. The Kinabatangan Ecosystem Health Project, Sabah, Malaysia

 

Monitoring ecosystem health is of vital importance to such an ecologically rich country as Malaysia. Close interaction between people and wildlife is a privilege of native Malaysians and tourists alike in Northern Borneo. Because it is a privilege that we wish to maintain, it is necessary to closely monitor the impact humans can have on animals, and vice versa. Human encroachment into previously un-impacted forest decreases the amount of available habitat and causes fragmentation with resultant increases in animal population densities and interactions among pathogens, vectors and hosts. Unfortunately, such a situation can facilitate disease transmission between human and animal and the emergence of novel infectious diseases.

 

Deforestation and agricultural encroachment are two forms of human-induced land use changes that can exacerbate infectious disease emergence. Emerging infectious diseases (EID’s) are those that have recently evolved, expanded in geographic range, changed in pathogenesis, and/or moved from one host species to another. Human contact with wildlife can facilitate the evolution of EID’s, which is something that needs to be carefully balanced with the needs of agricultural land and ecotourism. In fact over 75% of human diseases are zoonotic (transmitted between animals and humans), and the situation seems to be worsening from the impact of global environmental change. It is vitally important to quantify pathogen load in wildlife, livestock, and human communities within and along fragmented landscapes and closely monitor ecosystem health, for changes in such can improve decisions on land-use policy and benefit human and animal health alike.

 

Our project is a collaboration between myself, the Sabah Wildlife Department, the Malaysian Ministry of Health, and Drs. Marc Ancrenaz and Isabelle Lackman-Ancrenaz of the Kinabtangan Orang-utan Conservation Project. The goals of this project are:

1) Parasitological survey of the human populations (villagers and oil-palm plantation workers), wild orang-utans and elephants;

2) Hormonal correlates with intestinal parasite infection in the wild orang-utans;

3) Comparison of disease (parasite and virus) prevalence rates between populations with relatively high levels of contact with one another compared to those populations of humans and animals that are relatively isolated from one another.

4) Determination of changes in cortisol levels throughout the habituation process of wild orang-utans within the study site;

5) Analysis of cortisol responses in wild orang-utans following brief exposure to large groups of eco-tourists (participants in the Red Ape Encounters program).

6) Comparison of disease prevalence rates in orang-utans and elephants that occupy high population density forest fragments with those from low population density fragments.

 

Ultimately we strive to assess the likelihood of zoonotic disease transmission between animal and human populations in and around the Lower Kinabatangan Wildlife Sanctuary as well as determine the effects of habituation and subsequent stress on orang-utan and elephant health in the region.

2. Endocrine and Metabolic Responses to Immune Activation in College Students

Quantitative methods from endocrinology can be used to test predictions derived from evolutionary and theoretical biology. For example, advances in human female reproductive ecology demonstrate that ovarian function is highly sensitive to environmental factors, such as diet, activity patterns, infectious diseases, and psychological stress. As should be expected, female reproductive physiology can adapt to current environmental conditions in order to increase the likelihood of a successful reproductive event when the time is optimal. Unlike females, males do not undergo menstruation, gestation, childbirth, or lactation. In addition, metabolic investment in mammalian spermatogenesis is negligible, accounting for less than 1% of basal metabolic rate in human males. More taxing aspects of male reproductive effort include attracting a mate, competing with conspecifics for access to mates, protection and provisioning of offspring and mates, and physiological investments in the muscle tissues that augment mate attraction and competitive ability. High testosterone levels reflect investment in male reproductive effort through the ability to produce and maintain muscle tissue. However, high testosterone levels can compromise survivorship by increasing risk of prostate cancer, production of oxygen radicals, risk of injury due to hormonally-augmented behaviors such as aggression, violence and risk taking, negative energy balance from adipose tissue catabolism, and suppression of immune functions.

 

Testosterone-immunocompetence relationships have been assessed less frequently in humans compared to other species. However, evaluating immune-endocrine relationships has implications for understanding differences in disease severity, progression, and convalescence: evidence would suggest that individuals with high testosterone levels should be more susceptible to infection or require longer periods of convalescence. Therefore, changes in testosterone levels throughout the range of physiological variation may function as a basic aspect of human phenotypic plasticity and an adaptive response that facilitates the allocation of energetic resources towards either survivorship (immunocompetence; low testosterone levels) or reproductive effort (muscle anabolism; high testosterone levels). High testosterone may yield reproductive benefits, which would be balanced against increased susceptibility to infection. Depressed testosterone levels during illness may function, in part, to prevent immunosuppression caused  by higher testosterone levels as well as to suspend energetically-expensive anabolic functions.

 

Field studies on immune-endocrine interactions in humans are often complicated by the difficulty of identifying cohorts of individuals who are infected with a particular pathogen. For obvious ethical reasons, humans are not intentionally infected with pathogens. A novel approach and methodology involves assessing immune-endocrine interactions during the natural course of infection or immune activation in a large, localized population of college students.

 

Funded by the UWM Research Growth Initiative, myself and Dr. Julia Bonner (Director of the Norris Health Center) are assessing changes in metabolism, endocrine, and immune functions in a large sample of adult male college students naturally infected with influenza, cold virus, or other upper respiratory tract infection as well as students being vaccinated for Hepatitis B, influenza, rabies, meningococcus, and/or Yellow Fever.

 

This research will hopefully yield a fundamentally better understanding of testosterone-mediated immunity as well as endocrine and metabolic responses to immune activation. Formulating an explanatory framework for differential susceptibility to infectious diseases is quite valuable, and this research agenda has the potential for advancing clinical understanding of differential disease severity and recovery, as well as influencing treatment patterns for hypogonadism and disregulation of metabolism during illness.

3. Effects of Testosterone Supplementation on the Immune Functions of Obese Men and HIV-Infected Men

For males, testosterone is an anabolic steroid that regulates reproductive effort. However, testosterone can simultaneously alter immunocompetence (the ability of an organism to mount an effective immune response against invading pathogens. Thus, investigating the effects of testosterone on immune function in suitable human models allows for better understanding of the complex interrelationships of the immune and reproductive systems. Two such suitable models are HIV-infected men and obese men, both of which may exhibit lowered testosterone levels due to their medical states.

 

Under the direction of Drs. Shally Bhasin and Karen Herbst at Boston University Medical Center, the effects of androgen replacement therapy on muscle mass and quality of life measures are being investigated in HIV-infected men and obese men. However, the effects that testosterone supplementation may have on the immune functions of androgen-supplemented individuals have not been previously studied. That is, obese men can exhibit testosterone levels below normal, and testosterone supplementation appears to improve insulin sensitivity and decrease fat mass in abdominally obese men, yet the effects of altering testosterone levels on immune function in these men are unknown. Likewise, testosterone replacement may improve general health perceptions in HIV-infected men, and since weight loss (specifically of non-fat tissues) is a good predictor of survival, risk of hospitalization, and opportunistic infections in HIV-infected men, testosterone replacement therapy should be investigated.

 

Therefore, Drs. Bhasin, Herbst, and myself are currently assessing the effects of testosterone supplementation on cytokine ( TNF-alpha and IFN-gamma) levels and leukocyte counts in clinically obese men and HIV-infected men.

 

4. Parasitological analyses of fecal samples from children in rural Nepal (collaboration with Dr. Catherine Panter-Brick).

 

5. Parasitological analyses of fecal samples from wild baboon populations in Awash, Ethiopia (collaboration with Drs. Jane Phillips-Conroy and Clifford Jolly).

 

6. Identifying associations between testosterone and leukocyte counts in primate species using phylogenetic comparative analyses on the ISIS database (Collaboration with Dr. Charlie Nunn).

Featured Past Projects

 

1. Hormonal correlates with intestinal parasite load and dominance rank in wild male chimpanzees at Kibale National Park, Uganda (collaboration with Drs. David Watts and Pat Whitten).

 

 

 

 

 

2. Reproductive endocrine response to Plasmodium vivax infection in Honduran residents (collaboration with Drs. Jackeline Alger, Frank Cogswell, and Mark James).

 

 

 

 

 

 

 

 

3. Analyses of hormonal and immunological correlates in captive macaques infected with Venezuelan Equine Encephalitis, Yersinia pestis, and other infectious organisms, United States Army Medical Research Institute of Infectious Diseases (collaboration with Drs. George Ludwig, James Koterski, Frank Cogswell and Mark James).

 

 

4. Comparative developmental endocrinology of captive male macaques and baboons at Tulane National Primate Research Center (collaboration with Shelley Phillippi-Falkenstein, Mark Murchison, and Dr. Benjamin Campbell).

©2006 Michael Muehlenbein

The views expressed in this website do not necessarily reflect those of UWM.