I am a biological anthropologist interested in human evolutionary biology with special interest in human immunology. I received my Ph.D. in biology from the University of Buenos Aires (Argentina) in 1998. My main research goal is the study of the phenotypic diversity of the immune system and how different evolutionary forces have shaped (and shape) this diversity in different human populations. After moving to USA and during 2001-2005 I worked on different projects in molecular and cellular immunology with special attention to cytokines and T cell differentiation (Director: Dr. Rafael Fernandez-Botran, Department of Pathology and Laboratory Medicine, University of Louisville). From 2006-2010, I worked in collaboration with Dr. Manuel Casanova (Department of Psychiatry and Behavioral Sciences, University of Louisville) and Dr. Irene Litvan (Department of Neurology, University of Louisville) studying the role of inflammation on different brain disorders, like Autism, Alzheimer's disease, and Progressive Supranuclear Palsy.
Currently (2011-present), my main research project is to study the potential role of past pathogenic experiences in shaping the immune responses that we can detect in contemporary human populations.
Cytokine expression and the role of past epidemic events in shaping the immunological response in human populations
Cytokines are soluble immunomodulatory glycoproteins that are involved in the regulation of both physiologic and pathologic processes associated with inflammation, immune responses, and hemopoiesis. Changes in cytokine expression or activity can lead to alterations in these responses, for example enhancing or reducing inflammation. Cytokines and their receptors are often encoded by highly polymorphic genes, and some genotypes are responsible for the observed inter-individual differences in levels of cytokine production, and thereby constitute a mechanism for adaptive modulation of the immune response. Interestingly, in recent years, surveys using general continental-based samples have documented differences in the distribution of cytokine genetic polymorphisms among major human populations. Our preliminary analysis using a panel of different cytokine polymorphisms shows that within certain cytokines, the distributions of specific genotypes appear to be non-random and exhibit regional variation. Therefore from an evolutionary perspective, some populations may be undergoing a shift in the balance of pro- and anti- inflammatory cytokines. If natural selection played (and still does) an active role in shaping the cytokine expression make-up for different populations, which selective factor should be taken into consideration? Since cytokines are key components of the immune response and one of the main functions of the immune system is to mount an appropriate response against infective pathogens, we suggest that pathogens are the causal explanation for the distribution of cytokine polymorphisms in human populations.
The hypothetical evolutionary scenario proposed in this project is that after a long lasting epidemic event positive selection will impact those pro-inflammatory cytokines that mount an effective immune response against the pathogen. If immune mediator gene polymorphisms are associated with differential expression of key cytokines, we can expect that protective cytokine alleles will show an increased frequency still after the epidemic event is declined or eliminated, and this should be understood as a legacy of that epidemic event. Moreover, we can suggest that if there was a cytokine storm involved in the immune response during the epidemic event, today’s populations (descendants of those populations exposed to the long lasting pathogenic insult) will still reflect a strong inflammatory response, and one potential consequence of that is an over-expression of autoimmune and/or chronic inflammatory diseases.
My main research goal, bringing together different colleagues, is to test this hypothesis in different human populations (ancient and contemporary populations) using an interdisciplinary approach combining gene expression, genetic analysis (ancient and modern DNA), epidemiology and bioarchaeology.
However, research is not my sole professional goal. I am committed to pursue a career that combines teaching and research. Currently, I am teaching different courses about human evolution, human adaptation and human health from an evolutionary perspective. See "Teaching" for more information about my courses.
UNIVERSITY OF LOUISVILLE (USA)
- Introduction to Biological Anthropology(202): Spring/Fall & Online - DE
This course provides a general introduction to biological anthropology through an examination of the place of humans in the animal kingdom, the human evolutionary past, a comparative examination of human and primate behavior, and the dynamics of human variation. The course meets the General Education Program requirement for Natural Sciences. Students will demonstrate their ability to relate findings from paleoanthropology, primatology, and population genetics to general principles of evolution and biological diversity. Additionally, they will demonstrate their ability to apply these principles toward explaining questions of hominid evolution and contemporary human biological variation.
- Human Origins (303): Spring
The singular trajectory of human evolution presents patterns of genotypic and phenotypic variability that can be investigated by biological anthropologists. In this course you will learn about the common forces of evolution that shaped (and shape) both genotypic and phenotypic variability, explore the fossil record related to the evolution of Homo sapiens, and discuss current issues in the field of human evolution.
- Genes, People, and Evolution (305): Fall every other year
Where do we come from and to whom are we related? How can our genes help us to understand our evolutionary history? How has geography and history affected our genetic diversity? Human evolutionary genetics is the study of how one human genome differs from another and the implications of this for our understanding of our species in the past and present. Differences between genomes form the basis of anthropological, medical and forensic genetics. This course analyzes how we can use genetics to reconstruct individual ancestry and population history.
- Human Biological Variation (306): Fall every other year
People are biologically (and culturally) very diverse. We often think about these differences in terms of race or ethnic group. But we do not often think about these variations in terms of their evolutionary origin or their adaptive significance. Human variation can be visible (skin color, nose shape) or invisible (biochemical and molecular differences). Anthropologists and biologists have studied these variations for years and have attempted to understand why populations have different traits or have the same traits but in different frequencies. Now, new genetic and molecular evidence is changing the perspective of the understanding of our own biological variation. The main goal of this course is to study and discuss why the biological differences exist and how they help humans adapt to varying environments rather than oversimplify and document the differences creating racial categories.
- ·Human Adaptation (540): Fall every other year (Fall 2011)
This course explores and discusses biological strategies of human adaptation to different environments from an evolutionary perspective. The study of human adaptation emphasizes the plasticity of human responses to different environmental conditions, and this plasticity should be understood at the biological and behavioral level. However, current adaptations reflect present and past biological and behavioral processes. The central goal of this course is to understand how at multiple levels (anatomy, physiology, genetics, and behavior) human populations (past and present) respond to their surroundings. To achieve this goal, the course will be focused on human lifestyle changes and the corresponding adaptations (or misadaptations?) developed during and after the agriculture revolution.
Human Evolution in Health and Disease (650): Fall every other year (Fall 2010)
Our body is a bundle of trade-offs, shaped by different evolutionary forces in ancestral environments. The adaptations making us human were established to maximize our fitness but they were fixed during our evolutionary history and may not fit us as well at present time. Disease was, and is, one of the main selective forces shaping our biology, and it is necessary to study the relationship between our species and those diseases that were (and are) part of our evolutionary history. This course explores and analyses how human biology and evolution was and is shaped by life styles, health and disease. Human Evolution in Health and Disease is a seminar-style course.
UNIVERSITY OF BUENOS AIRES - Facultad de Ciencias Exactas y Naturales (Argentina):
- Genes and Fossils: Introduction to Human Evolution (Graduate course): June or July --> Link to course material (Spanish)
Fernandez-Botran, R; Ahmed, Z; Crespo, F; Gatenbee, Ch; Gonzalez, J; Dickson, D; and Litvan, I. 2011. Cytokine expression and microglial activation in brains of progressive supranuclear palsy and Alzheimer’s disease patients. Parkinsonism & Related Disorders 17: 683-688.
- Crespo, F.; Fernandez-Botran, R.; Tillquist, C.; Sears, L.; Mott, M. & Casanova, M. 2009. Cytokine polymorphisms in autism: Their role in immune alterations. In "Autism: Oxidative Stress, Inflammation and Immune Abnormalities" Edited by Abha Chauhan, CRC Press, Taylor and Francis Publishers: 315-324.
- Ihenetu, K.; Qazzaz, H.; Crespo, F.; Fernandez-Botran, R.; and Valdes, R. 2007. Digoxin-Like Immunoreactive Factors (DLIF) Induce Apoptosis in Human Acute T-Cell Lymphoblastic Leukemia. Clinical Chemistry 53(7): 1315-1322.
- Crespo, F.; Sun, X.; Cripps, J.; & Fernandez-Botran, R. 2006. The immunoregulatory effects of gangliosides involve immune deviation favoring type-2 T cell responses. J. Leukocyte Biol. 79:586-595.
- Lauria de Cidre, L.; Crespo, F.; & Aldana Marcos, H.J. 2006. Morphologic, Histochemical and Immunohistochemical Characterization of Tracheobronchial Respiratory Glands in South American Sea Lion Otaria flavescens (Pinnipedia Mammalia). Journal of Histotechnology 29(1): 29-35.
- Crespo, F. & Lauria de Cidre, L. 2005. Functional significance of bronchial sphincters in two Southwestern Atlantic dolphis: Pontoporia blainvillei and Lagenorhynchus obscurus: a comparative approach. Mammalia 69(2): 233-238.
- Cripps, J.G.; Crespo, F.; Romanovskis, P.; Spatola, A.F.; Fernandez-Botran, R. 2005. Modulation of acute inflammation by targeting glycosaminoglycan-cytokine interactions. Intl. Immunopharmacol. 5(11):1622-1632.
- Fernandez-Botran, R.; Crespo, F. & Sun, X. 2002. Soluble cytokine receptors in biological therapy. Exp. Opin. Biol. Ther. 2(6):585-605.
- Fernandez-Botran, R.; Gorantla, V.; Sun, X.; Ren, X.; Perez-Abadia, G.; Crespo, F.; Oliver, R.; Orhun, H.; Quan, E.; Maldonado, C.; Ray, M. & Barker, J. 2002. Targeting of glycosaminoglycan-cytokine interactions as a novel therapeutic approach in allotransplantation. Transplantation 74(5):623-629.