Texas Biomed Science Report 2011-2012 - Texas Biomedical ...

Melanie Carless, Ph.D.
Assistant Scientist, Genetics
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, her 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
of 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
Staff
Left to right: Jennifer Neary, Sarah
Heltzel, Melanie Carless, Hemant
Kulkarni, Kara Peterson, Jessica Valdez
2011–2012 Scientific Report
“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.”
Publications
• Dasgupta P, Rizwani W, Pillai S, Kinkade R, Rastogi S, Banerjee S, Kovacs M, Carless M,
Kim E, Haura E, Coppola D, Chellappan S (2009) Nicotine induces cell proliferation, invasion
and epithelial-mesenchymal transition in a variety of human cancer cell lines. Int J Cancer
124:36-45.
• Prior MJ, Foletta VC, Jowett J, Segal DH, Carless MA, Curran JE, Dyer TD, Stern MP, Moses
EK, Collier GR, Blangero J, Walder KR (2010) Abelson Helper Integration Site-1 is a
candidate gene for insulin resistance and type 2 diabetes. Metabolism 59:1057-64.
• 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 (2010) Genetic control over the
resting brain. Proc Natl Acad Sci USA 107:1223-8.
• Gawrieh S, Baye TM, Carless M, Wallace J, Komorowski R, Kleiner DE, Andris D, Makladi B,
Cole R, Charlton M, Curran J, Dyer TD, Charlesworth J, Wilke R, Blangero J, Kissebah AH,
Olivier M (2010) Hepatic gene networks in morbidly obese patients with nonalcoholic fatty
liver disease. Obes Surg 20:1698-709.
• Carless MA, Glahn DC, Johnson MP, Curran JE, Bozaoglu K, Dyer T, Winkler A, Cole S,
Almasy L, MacCluer J, Duggirala R, Moses E, Goring HHH, Blangero J (2011) Impact of DISC1
variation on neuroanatomical and neurocognitive phenotypes. Mol Psychiatry 16:1096-104.
• Glahn DC, Curran JE, Winkler AM, Carless MA, Kent JW Jr, Charlesworth JC, Johnson MP,
Göring HH, Cole SA, Dyer TD, Moses EK, Olvera RL, Kochunov P, Duggirala R, Fox PT,
Almasy L, Blangero J (2011) High dimensional endophenotype ranking in the search for
major depression risk genes. Biol Psychiatry: Epub ahead of print.
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.
E For more information, please visit www.txbiomed.org/departments/
genetics/genetics-staff-bio?u=128
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