Ana Cristina Leandro, PhD

Research Focus

Dr. Ana Leandro is an Immunologist with more than 15 years of experience in the clinical research of infectious diseases, predominantly in Mycobacterium tuberculosis. Her research focused on the immunopathogenesis of tuberculosis, and she was interested in the identification and characterization of susceptibility genes for this disease with the ultimate objective of gaining an insight into the biological pathways involved in disease pathogenesis. She has extensive experience in several immunological, pathological and microbiological technologies and most recently in high-throughput genomic technologies and applying those to help understand the genetic underpinnings of disease. As a Co-I on a several projects, she has continued to significantly enhance her expertise in several other immunological and molecular techniques predominantly using high-throughput omics.

In 2006, Dr. Leandro immigrated to the United States to work on the development of a DNA vaccine against tuberculosis in non-human primates at the Texas Biomedical Research Institute. She assisted the PI with compiling an NIH R01 grant entitled “TB vaccine development in Nonhuman Primate Model,” which was awarded $3.8 million. She oversaw and worked on all laboratory aspects of this project. She was able to gain insight and expertise in several project aspects: technological experience, project management and data analysis.

Recently, her research efforts and expertise are in the molecular and functional aspects of gene identification for complex diseases. She is involved in several projects where she manages the molecular components, being responsible for the phenotyping and sequencing of sample from several complex diseases such as cardiovascular disease, type 2 diabetes, bipolar disease and Alzheimer’s disease. She has also played a major role in a few large-scale human genetic projects in the STDOI. She generated quality data for several studies, trying to understand the influence of host genetics in susceptibility to complex diseases. She is also working with epigenetic influences on Alzheimer’s disease. Her role as a PI on this project was being responsible for the overall project, including bisulfite conversion of the DNA, running the methylation arrays, and performing the statistical analyses.

For the last two and a half years, She has been working with exposome, lipidomics, metabolomics, and metallomics. She is focused on the directly measured pollutome component of the Major Depressive disorder (MDD) exposome. Her team's goal is to use a novel genomic approach to improve the search for environmental determinants of MDD to provide a more complete conceptualization of the illness, facilitating treatment and prevention. Her and her team will use their extended Mexican-American pedigrees, high-throughput pollutomics/metallomics, and novel statistical analyses for the possible identification and understanding of the pollutant-influenced pathways and mechanisms contributing to MDD risk in Mexican Americans.

Epigenetic influences on Alzheimer’s disease risk

Ana Cristina Leandro, Ph.D.

Age is considered one of the greatest risk factors for the development of Alzheimer’s disease (AD), with the likelihood of developing AD increasing exponentially with age, doubling every 5 years after age 65. While the reason for this is still unknown, the etiology of AD and its relationship with age are both likely the result of an intricate interplay between genetic, epigenetic, and environmental factors. Differential methylation of sites across the genome has been implicated as a contributor to variation in risk, severity, and progression of AD. In addition to being affected by both genetic and environmental factors, variation in global DNA methylation levels has been shown to have a complex relationship with aging. Indeed, epigenetic changes have been shown to be one of the hallmarks of aging.

A number of studies of the relationship between DNA methylation and AD risk are ongoing but there currently are no published reports of the phenomenon in Hispanic populations. This pilot study is a first step toward addressing that gap in knowledge.   

To do this the investigator will take advantage of existing biomaterials and data from the Maracaibo Aging Study (MAS), directed by Dr. Gladys Maestre. More than 800,000 genome-wide methylation sites will be evaluated at single-nucleotide resolution in existing white blood cell samples from 24 AD cases and 24 unaffected sex and age matched controls. There are two specific aims. The first aim is to identify quantitative methylation profiles that distinguish the AD cases from the unaffected controls. The second is to identify methylated sites that show the greatest differences between the two groups, generate epigenetic clock-based ages, and compare AD cases and controls.  

This project’s ultimate objective is to generate novel data that will serve as valuable preliminary results in a subsequent application for extramural funding of a more extensive and intensive study of epigenetic influences on the relationships between age and AD risk, severity, and progression in a Hispanic population. Because DNA methylation is to a degree responsive to other environmental stressors the results of this pilot study can also serve as preliminary data for investigations of the interplay between age, epigenetics and socioeconomic, socio-behavioral, and socio-environmental factors in AD.