James A. Knowles MD, PhD
Professor of Psychiatry & the Behavioral Sciences

Jim Knowles was recruited to the Department of Psychiatry & the Behavioral Sciences from Columbia University in July 2006.  He was recently promoted to the rank of full professor with tenure. He is a member of the Zilkha Neurogenetic Institute and his lab is located on the 4th floor of ZNI. He lives in Altadena with his wife Valerie (an OR nurse at USC University Hospital), a pair of monozygotic twin daughters and a dog, cat, green-winged macaw, rabbit and hamster.

What are your research interests?

My research focus is human genetics, with a special interest in the genetic basis of the psychiatric disorders.

How did you come to pursue your current research interests?

In 9th grade, I was fortunate to take a molecular biology class and a genetics class.  Learning about John Gurdon’s experiments with Xenopus, I became fascinated with genetics.  Later, when I couldn’t decide whether to go to graduate school or to medical school, I chose to do both.  Because of my interest in behavior, a residency in Psychiatry seemed a logical choice.

Briefly, what are some of your current research projects?

My group has a number of different projects ongoing, and all of these are collaborative projects.  In addition to looking at the Mendelian genetics of primary pulmonary hypertension, we are also looking at several complex genetic disorders including obsessive-compulsive disorder, opiate addiction, nicotine addiction, panic disorder, and early-onset recurrent major depression.  We also have collaboration with Drs. Carlos and Michele Pato, in which we are investigating the genetics of both schizophrenia and bipolar disorder. The exciting thing right now is our ability to do DNA sequencing on a scale that was unimaginable 5 years ago.  In addition to the whole human genome sequencing we are doing, I am very excited by the relatively inexpensive whole exon sequencing we are piloting.  Using this approach, I think we could find new disease genes for a wide range of the disorders that we see in our clinics and hospitals at the KSOM, and I welcome new clinical collaborations with interested faculty.  With recent new funding, we hope to see USC become a leader in genomic medicine.

How do you balance your different research, teaching, clinical, and administrative roles?

I am fortunate to be able to devote the majority of my time to research.  I have few administrative duties, other than some departmental duties and running a lab. At the moment, the clinical relevance of findings in psychiatric genetics are unclear, so there is not much clinical need for my expertise, but I expect that will change over the next decade.  I also enjoy teaching residents about genomics. Currently my lab is comprised of 2 assistant professors, 1 post-doc, 4 technicians, a programmer, and 2 high school students.  We often have additional students (including medical students) spending time in the lab as well.

What brought you here to USC and what do you like about being here?

Over the years, I had always enjoyed interacting with Carlos and Michele Pato at meetings and conferences, and when they moved here, they invited me to visit USC.  Since I had spent all my time in New York up until that point, I felt it was a good time for a change.  I enjoy the collaborative nature of the faculty here at USC, which makes for a productive environment.  I am very excited about the investment in resources for genetics and genomics that has been occurring at the Keck School.  We are just getting two Illumina GAIIx’s installed today and a third in a few weeks, so when combined with the two already in place at the Epigenome Center and the additional one they are buying, the Keck School has a significant genomics program in place.

How do you enjoy living in Southern California? 

Naturally I enjoy the excellent weather, and the proximity to both the ocean and to the mountains.  This allows me to enjoy my main hobbies –competitive sailing and skiing.

Key Publications

International Schizophrenia Consortium, Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009 Aug 6;460(7256):748-52. Epub 2009 Jul 1.

Rosenzweig EB, Morse JH, Knowles JA, Chada KK, Khan AM, Roberts KE, McElroy JJ, Juskiw NK, Mallory NC, Rich S, Diamond B, Barst RJ. Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension. J Heart Lung Transplant. 2008 Jun;27(6):668-74. Epub 2008 Apr 9.

Lachman HM, Fann CS, Bartzis M, Evgrafov OV, Rosenthal RN, Nunes EV, Miner C, Santana M, Gaffney J, Riddick A, Hsu CL, Knowles JA. Genomewide suggestive linkage of opioid dependence to chromosome 14q. Hum Mol Genet. 2007 Jun 1;16(11):1327-34.

Levinson,D.F., Evgrafov,O.V., Knowles,J.A., Potash,J.B., Weissman,M.M., Scheftner,W.A., DePaulo,J.R., Jr., Crowe,R.R., Murphy-Eberenz,K., Marta,D.H., McInnis,M.G., Adams,P., Gladis,M., Miller,E.B., Thomas,J., and Holmans,P. (2007). significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers. American Journal of Psychiatry 164, 259-264.