Texas Biomed Staff

Melanie Carless

Assistant Scientist | Genetics
Phone: 210-258-9766
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Summary

Although researchers are beginning to make progress in understanding the biological mechanisms that drive complex disease development, many areas of study are only just starting to be explored. Epigenetic mechanisms, such as genomic methylation and microRNA regulation, are now being seen as significant players contributing to the development of complex diseases, although how these factors integrate with our genetic architecture is not well understood. Carless’s research focuses on identifying epigenetic variation that contributes to the development of various complex diseases and how these changes might influence and interact with genetic variation to propel disease progression. 

Carless is investigating how changes in microRNA expression regulate gene expression to influence variation in neuroanatomical and neurocognitive endophenotypes, and how this variation might play a role in psychiatric disorders. Recently, Carless’s laboratory has identified several microRNAs whose expressions are both heritable and appear to influence neuroanatomical traits associated with depression. In addition, Carless and her colleagues have uncovered evidence that genomic methylation within a number of genes is correlated with many metabolic syndrome-related phenotypes, such as measures of obesity, blood pressure and insulin and glucose levels; as well as with neuroanatomical and neurocognitive traits. Carless has also continued to assess the role genetic variation in depression and neurological traits, identifying several variants within an important psychiatric-related gene that contribute to differences in neuroanatomical and neurocognitive traits.

Carless believes that it is essential to gain a better understanding of both genetic and epigenetic factors driving the development and progression of mental disorders, heart disease and cancer in order to identify appropriate biological targets for better therapeutic intervention. Recent advances in the field have resulted in the development of therapeutics that specifically target methylation and microRNA expression. It is hoped that the reversal of deleterious changes will lead to a return of normal genetic regulation. Her work aims to advance the current knowledge of epigenetic involvement in complex diseases and determine interactions that influence genetic regulation to identify novel targets for drug development.

Education

Doctoral Degree: Molecular Genetics

Griffiths University Gold Coast , Australia

Postdoctoral Work

2004-2006   Moffitt Cancer Center, Tampa, FL

2006-2008   Texas Biomedical Research Institute, San Antonio, TX

Research Focus

The focus of our work is in identifying epigenetic events that contribute to the development of complex diseases. By merging findings from both genetic and epigenetic studies, we hope to better delineate the biological mechanisms that drive the development of psychiatric disorders, heart disease and cancer, thus identifying novel targets for drug development.

Awards and Honors

2009                Early Career Investigator Award, World Congress of Psychiatric Genetics
2009                NARSAD Young Investigator Award
2007                Travel Grant – World Congress of Psychiatric Genetics XV
2003                Travel Grant – Queensland Cancer Fund
2003                Travel Grant – Griffith University International Conference Grant

Publications

Genetic control over the resting brain.

Glahn DC, Winkler AM, Kochunov P, Almasy L, Duggirala R, Carless MA, Curran JC, Olvera RL, Laird AR, Smith SM, Beckmann CF, Fox PT, Blangero J.
Proc Natl Acad Sci U S A 107 (3): 1223-1228, 2010
PubMed ID: 20133824

Analysis of genomic aberrations using comparative genomic hybridization of metaphase chromosomes.

Carless M.A.
Methods in Molecular Biology 523: 177-202, 2009
PubMed ID: 19381938

Grants

5 R01 MH078111-04 (Blangero)    07/01/06 - 06/30/11    1.20 calendar
NIH/NIMH    $461,991
Genetics of Brain Structure and Function
The major goal of this project is to localize and identify genes influencing human brain structure and function. Role: Co-Investigator

5 R01 HL070751-08 (Almasy)    03/15/07 - 11/30/11    0.60 calendar
NIH/NHLBI     $303,696 (1yr NCE)
Genetic Analysis of Idiopathic Thrombosis
The major goal of this project is to identify the genetic variance influencing hemostasis phenotypes. Role: Co-Investigator

5 R01 AG031277-02 (Williams-Blangero)    02/15/08 - 01/31/13    3.00 calendar
NIH/NIA    $316,871    
Genetic Determinants of Human Transcriptional Aging
The major goal is to identify novel genes involved in human biological aging process. Role: Co-Investigator

5 R01 MH083824-03 (Glahn)    10/01/08 - 02/28/13    0.60 calendar
NIH/NIMH    $140,781
Genetics of Brain Structure and Function: Genome-Wide Association
The major goal of this project is to identify genes and genetic variation that influences human brain structure and function, using a genome-wide association approach. Role: Co-Investigator

5 R01 MH085950-01 (Carless)    04/01/10 - 12/31/14    4.20 calendar        
NIH/NIMH     $306,415    
Identification of Novel MicroRNAs Associated With Brain Structure and Function
The major goal of this project is to identify microRNAs whose expression is associated with neurocognitive and neuroanatomical phenotypes and investigate their potential involvement in psychiatric disorders. Role: Principal Investigator

5 R01 DK087749-01 (Carless)    05/20/10 - 04/30/15    2.40 calendar    
NIH/NIDDK    $355,314    
Large-Scale Methylation Profiling in Metabolic Syndrome Phenotypes
The major goal of this project is to investigate the consequences of genomic methylation on phenotypes related to metabolic syndrome in Mexican American and Caucasian individuals. Role: Principal Investigator

Voelcker Foundation (Carless)        03/01/10 – 02/28/11        0.00 calendar
        $40,000
Investigation of a potential therapeutic molecule targeted at miRNA induced gene regulation
This study is aimed at identifying in vitro miRNA targets and developing a LNA-antimiR for potential use in treating acute myeloid leukemia. Role: Principal Investigator

Southwest Foundation Forum (Carless)     10/01/09 – 03/31/11        0.00 calendar
    $34,871
Characterization of the Neurite Outgrowth Gene, SLITRK6, and its’ Role in Human Brain Structure
This study is aimed at characterizing the SLITRK6 gene via gene resequencing, genotyping and functional analysis to determine variation associated with altered brain structure. Role: Principal Investigator

Joe & Jesse Crump Foundation (Carless)    07/01/09 - 6/30/11        0.00 calendar
    $47,700
Genetic Variation Associated with Acute Myeloid Leukemia and Myelodysplastic Syndrome
This study is aimed at identifying genetic variation that contributes to the development and treatment response of acute myeloid leukemia and myelodysplastic syndrome. Role: Principal Investigator

Voelcker Foundation (Carless)        10/01/09 - 09/30/11        0.00 calendar
    $49,891    
Epigenetic Variation Contributing to Myelodysplastic Syndrome and Acute Myeloid Leukemia
This study is aimed at determining epigenetic regulation involved in the development of acute myeloid leukemia and myelodysplastic syndrome. Role: Principal Investigator

Young Investigator Award (Carless)        01/01/10 – 12/21/12        0.00 calendar
NARSAD    $59,500
Transcriptional profiling in bipolar I disorder
This study is aimed at determining gene expression profile differences between bipolar individuals with or without psychosis and their unaffected siblings and control subjects. Role: Principal Investigator