Genomics is allowing the discovery of thousands of new genes and the
development of high throughput technologies. Nowadays, several fields
in biology have become sciences that demand generating and processing
massive amounts of molecular data; epidemiological investigations are
not an exception.
Regardless of these technological innovations, the concepts and nature
of the questions investigated by public health researchers and planners
are still the same: How do clinical end points relate with parasite
genetic variants? What level of efficacy can be expected from a new
intervention strategy? How does drug resistance emerge? What is the
impact of transmission pressure on the dispersal of drug resistant parasites?
How variable is a specific antigen? How did this pathogen originate? These
questions require the analysis of molecular data to assess temporal and
spatial patterns: this is the field of molecular evolutionary biologists.
However, evolutionary biologists would interpret these questions as
follows: How does natural selection favor the fixation of a given
mutation? What is the gene flow among populations? What are the phylogenetic
relationships of the parasites? What is the genetic structure of a given
population? What are the co-evolutionary dynamics between the parasite
and host genetic diversities? Do the intra-host dynamics relate to virulence?
These two perspectives cannot be reduced to semantic discrepancies.
Nevertheless, understanding the extent and driving mechanisms behind
the maintenance of genetic diversity in infectious disease agents is
becoming a matter of great interest. Public health researchers face
it wherever control strategies are deployed or tested; evolutionary
biologists, on the other hand, find it an issue of tremendous relevance
as it relates to the origin of local adaptations in geographically
differentiated populations, as well as, the origin of novel
interspecies interactions.
My current research focuses on molecular evolutionary biology of human
and primate malaria parasites. Malaria is endemic in most of the tropical
and subtropical ecosystems worldwide and exhibits great geographic diversity.
In addition to basic evolutionary biology issues, I am involved in molecular
epidemiology studies such as outbreak investigations, the design of
epidemiologic surveillance programs in malaria drug resistance, and
the effect of intervention strategies on malaria parasite populations.
The specific aims of my ongoing research are (1) to study the mechanisms
involved in the maintenance of genetic polymorphisms in natural populations
of malaria parasites, (2) to assess the effect of the local ecology on the
parasite population structure as it relates with the emergence of drug
resistance and antigenic diversity, (3) to study the effect of positive
natural selection and codon bias on the long-term evolution of proteins
and (4) to assess the phylogenetic relationships among primate malaria
parasites in order to understand their origin and speciation, including
those species parasitic to humans. I maintain active collaborations with
the Centers for Disease Control and Prevention (Atlanta, Georgia), and
colleagues in endemic countries.
My long-term goal is to develop a program on disease ecology and
evolution focusing on human and wildlife parasites. Although I
consider historical and geographic patterns, I am inclined to study
specific phenotypes. I believe that the study of complex phenotypes
such as virulence, drug resistance, and antigenic variation require
multidisciplinary approaches that integrate epidemiology, immunology,
molecular biology, population genetics and ecology. Such levels of
integration can be accomplished within the theoretical framework provided
by evolutionary biology.
Selected Publications
Escalante AA, Cornejo OE, Freeland DE, Poe AC, Durrego E, Collins
WE, Lal AA (2005) A monkey's tale: The origin of Plasmodium vivax
as a human malaria parasite. Proc Nat Acad Sci USA 102: 1980-85.
Escalante AA, Cornejo OE, Rojas A, Udhayakumar V, Lal AA. (2004)
Assessing natural selection in malarial parasites. Trends Parasitol
20:388-95
Escalante AA, Grebert HM , Isea R, Goldman IF, Basco L, Magris M,
Biswas S, Kariuki S, Lal AA (2002) A study of genetic diversity in
the gene encoding the circumsporozoite protein (CSP) of Plasmodium
falciparum from different transmission areas. Mol Bioch Parasitol 125: 83-90.
Escalante AA, Grebert HM, Chaiyaroj SC, Magris M, Biswas S, Nahlen
BL, Lal, AA (2001) Polymorphism in the gene encoding the Apical
Membrane Antigen-1 (AMA-1) of Plasmodium falciparum VI Asembo Bay
Cohort Project. Mol Bioch Parasitol 113: 279-87.
Escalante AA, Freeland DE, Collins WE, Lal AA (1998). The evolution
of primate malaria parasites based on the gene encoding cytochrome b
from the linear mitochondrial genome. Proc Nat Acad Sci USA 95: 8124-29.
Escalante AA, Lal AA, Ayala FJ (1998) Genetic Polymorphism and Natural
Selection in the Malaria Parasite Plasmodium falciparum. Genetics 149:189-202.
Wolfe ND, Escalante AA, Karesh WB, Kilbourn A, Spielman A, Lal AA
(1998) Wild Primate Populations In Emerging Infectious Disease Research:
The Missing Link? Emerging Infectious Diseases 4:149-58.
Escalante A, Ayala FJ (1994) Phylogeny of the malarial genus Plasmodium,
derived from ribosomal gene sequences. Proc Nat Acad Sci USA 91:11373-77.
