Melanie A. Carless

Melanie A. Carless, Ph.D.

Associate Professor | Population Health

Research Focus

Dr. Carless works on genetic and epigenetic factors that drive the development and progression of heart disease and mental disorders. Her work aims to advance the current knowledge of epigenetic involvement in complex diseases and understand interactions that influence genetic regulation. This will help to identify novel targets for drug development and better therapeutic intervention.

  • Role of DNA methylation on obesity and metabolic syndrome
  • Genetic effects on migraine
  • Gene expression and DNA methylation changes associated with schizophrenia, bipolar disorder, depression and associated neuropsychiatric traits
  • Role of microRNAs and microRNA variants in psychiatric diseases (schizophrenia, bipolar disorder, depression, PTSD, and associated neuropsychiatric traits)
  • Effect of microRNAs on gene expression
  • Understanding psychiatric disorders through induced pluripotent stem cells

Dr. Carless has more than 15 years of experience working in molecular genetics.

Inside The Lab

Epigenetic mechanisms, such as DNA methylation and microRNA regulation, are now considered significant players in the development of complex diseases, although the integration of these factors with our genetic architecture is not well understood. Our lab studies epigenetic variation that contributes to complex disease development and the role of this variation in the genetic-transcriptomic paradigm.

In collaborative efforts, we generated genome-wide genotyping and gene expression data for the San Antonio Family Study (SAFS) to investigate genes involved in cardiovascular- and psychiatric-related phenotypes. One of our findings implicates a novel genetic region associated with intima-media thickness, a risk factor for cardiovascular disease. We have also generated epigenome-wide DNA methylation profiles in our investigation of metabolic syndrome and related phenotypes within the SAFS, identifying several genes whose DNA methylation levels are associated with diabetes, obesity and dyslipidemia. Further study of the gene TXNIP, crucial for regulation of glucose and lipid homeostasis, suggests its specific role in the onset of diabetes.

Our studies demonstrated the importance of genetic variation in the expression of the DISC1 gene, a well-known risk gene for schizophrenia and bipolar disorder, and identified variation that influences brain structure, suggesting a mechanism by which the gene may act to influence psychiatric disorders.

Using next-generation sequencing within the SAFS cohort, we identified a potentially novel microRNA, nominally associated with brain structure phenotypes involved in memory. We continue to research the role of microRNAs in psychiatric disease by investigating cohorts involving schizophrenia, bipolar disorder, major depressive disorder and post-traumatic stress disorder.

Other collaborative efforts led to the generation of transcriptional data to identify markers of adiposity, hypertriglyceridemia, cardiovascular disease risk metabolic syndrome, fatty liver disease, migraine, bipolar disorder and schizophrenia.

To determine the functional impact of genetic and epigenetic variation on the development of novel therapeutics and delivery methods, we are conducting pilot studies to establish induced pluripotent stem cell lines and differentiated neuronal cells from adolescents with bipolar disorder. Here we aim to understand potential delivery mechanisms for small biological molecules.

We are also working on establishing new methodologies to study the effect of microRNAs on gene and protein expression on a genome- wide scale.

Many of our recent genetic and epigenetic findings point to the importance of ethnic-specific variation and risk, solidifying the need to study minority cohorts.

Main Technologies And Methods Used

  • Illumina next-generation sequencing — whole genome sequencing, exome sequencing, RNA-Seq, miRNA-Seq, Methyl-Seq
  • Pyrosequencing
  • Methylation-based PCR
  • Microarray analysis
  • Transcriptional profiling
  • Genotyping
  • Cell culture and cell-based assays
  • Functional analysis