The Kumar Lab
Studies neural circuits in the brain and associated behavioral abnormalities.
Studies neural circuits in the brain and associated behavioral abnormalities.
For circadian behavior, mutagenesis screens have identified core regulators of the autoregulatory feedback loop, such as Clock and Period. Although much is known about the circuitry that regulates motivation and reward behaviors, forward genetic approaches have not been widely applied to dissect these behaviors in mice. This leaves open the possibility of discovering novel genes, alleles and pathways that regulate these behaviors. Using high-throughput screening to discover mutants for acute cocaine response and open-field behavior, we have developed a collection of cocaine-response and open-field behavioral mutants that we are characterizing. We have genetically mapped three of these lines and are performing next-generation sequencing to identify the causative mutation. We have also used QTL analysis of two closely related mouse substrains to identify a novel gene, Cyfip2, that regulates cocaine response. Using genetics as its foundation, and a combination of biochemistry, physiology and imaging techniques, we dissect complex behavior in mammals.
As part of the NIH Neurogenomics project (Vitaterna, Pinto and Takahashi, 2007) we screened 10,000 mice per year for five years in six phenotypic domains. Vivek led the psychostimulant response screen in which acute response to cocaine was measured as a locomotor output assay. He developed a high throughput video-based screening facility capable of testing 96 mice per day with only one technician, in a 1.5 hour combined open-field and psychostimulant response assay. At UT Southwestern Vivek conducted a second-generation screen that had a 10-fold increase in detection of true positive mutants (Takahashi, Shimomura and Kumar, 2008, Kumar et. al., 2011). Through these two screens, the Kumar Lab has a panel of mutants that we are characterizing and positionally cloning. Some of the mutants are described at Kumarlab.org.
Utilizing quantitative genetics and positional cloning with two closely related mouse substrains, C57BL/6J (B6J – The Jackson Laboratory) and C57BL/6N (B6N – NIH), we have identified Cytoplasmic FMRP Interacting Protein 2 (Cyfip2) as a key regulator of cocaine response in mammals. This work has three major implications. First, we identified a mutation at the nucleotide level utilizing QTL analysis and provided genetic, biochemical and physiological evidence that CYFIP2 is a regulator of acute and sensitized cocaine response. Second, with over 20 commercially available C57BL/6 substrains, many with known behavioral differences, we describe a framework to utilize mouse substrains as a rich genetic source for discovering new genes and alleles that regulate behavior. If other substrains such as C3H/He and DBA/2 are included, hundreds of mouse substrains, many with known phenotypic differences, are available for analysis. Third, as the phenotyping phase of IKMC begins, care must be taken when comparing new behavioral data from B6N substrains with existing data from B6J, particularly for behavioral phenotypes (Kumar et. al., Science 2013).
Research Highlight
December 01, 2016
Researchers at JAX and the University of Texas Southwestern Medical Center have identified two genes that play significant roles in maintaining regular sleep.
Blog Post
June 06, 2016
JAX Associate Professor Vivek Kumar, Ph.D., explains why opioid users who have recently been released from prison or those who have already detoxed are more likely to overdose than new drug users.
Blog Post
February 03, 2016
Addiction is a chronic illness, with genetic, environmental and social aspects that are similar in scope to illnesses such as diabetes. Why should one be treated as a social and moral failure while the other is a medical issue?
Vivek Kumar, Ph.D., has a background in neuroscience and specializes in addiction research. He will be joining the JAX faculty in late 2014.
The Search Magazine Article
May 23, 2017
Rather than treating addiction as a personal failure, Assistant Professor Vivek Kumar, Ph.D., shows how genetics prove addiction to instead be a chronic brain disease.
The Search Magazine Article
December 06, 2016
Recent program at JAX focused on treating addiction as a chronic illness with genetic, environmental and social aspects, and sharing the latest efforts toward prevention, treatment, and law enforcement initiatives.
Press Release
June 20, 2016
JAX Assistant Professor Vivek Kumar will use the five-year grant to pinpoint genetic variants that increase susceptibility to addiction.
Blog Post
December 22, 2015
More than 350 million people are affected by depression, making it one of the most common disorders that affect humans worldwide. During the last decade, increased access to brain imaging technology has allowed neuroscientists and hospital clinicians to view the brain in detail to measure neural activity and quantify neurotransmitter levels. These studies have revealed many clues regarding the underlying contributing factors of depression and the pathophysiology of this disease.