Stavros Lomvardas, Ph.D.
Our research program aims to understand the molecular mechanisms of olfactory receptor gene choice. Olfactory receptor (OR) genes compose the largest mammalian gene family consisted of more than 1000 members. These genes are expressed in a stochastic and mutually exclusive fashion in such a way that only one OR allele is expressed in each olfactory sensory neuron. Our data suggest that this unusual expression pattern is orchestrated by a combination of positive and negative regulatory mechanism. According to our findings, OR genes undergo chromatin mediated silencing at a developmental stage that precedes olfactory receptor activation. One of the 3000 alleles is chosen for activation, by the enzymatic removal of the silencing chromatin marks. We currently combine genetic and biochemical approaches that together with cutting edge microscopy should reveal critical mechanistic details of this process.
2002 Harold M. Weintraub Award for outstanding achievement during graduate studies in Biological Sciences
2002 Samuel W. Rover and Lewis Rover Awards for outstanding achievement in Biochemistry and Molecular Biophysics
2003-2006 Helen Hay Whitney Foundation Fellowship
2009-2014 NIH Director's New Innovator Award
2009-2011 Rett Syndrome Research Trust, New Investigator Award
2010-2011 Hellman Family Award for Early-Career Faculty (UCSF)
2010-2014 NIH EUREKA
2010-2015 NIH Roadmap for Epigenomics
Dalton RP, Lyons DB, Lomvardas S. Co-Opting the Unfolded Protein Response to Elicit Olfactory Receptor Feedback. Cell. 2013 Oct 10;155(2):321-332.
Colquitt BM, Allen WE, Barnea G, Lomvardas S. Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons correlates with changes in gene expression and cell identity. PNAS. 2013 Sep 3;110(36):14682-7.
Lyons DB, Allen WE, Goh T, Tsai L, Barnea G, Lomvardas S. An epigenetic trap stabilizes singular olfactory receptor expression. Cell. 2013 Jul 18;154(2):325-36.
Clowney EJ, LeGros MA, Mosley CP, Clowney FG, Markenskoff-Papadimitriou EC, Myllys M, Barnea G, Larabell CA, Lomvardas S. Nuclear aggregation of olfactory receptor genes governs their monogenic expression. Cell. 2012 Nov 9;151(4):724-37.
Clowney EJ, Magklara A, Colquitt BM, Pathak N, Lane RP, Lomvardas S. High-throughput mapping of the promoters of the mouse olfactory receptor genes reveals a new type of mammalian promoter and provides insight into olfactory receptor gene regulation. Genome Research. 2011 Aug;21(8):1249-59.
Magklara A, Yen A, Colquitt BM, Clowney EJ, Allen W, Markenscoff-Papadimitriou EC, Evans ZA, Kheradpour P, Mountoufaris G, Carey C, Barnea G, Kellis M, Lomvardas S. An Epigenetic Signature for Monoallelic Olfactory Receptor Expression. Cell. 2011 May 13;145(4):555-70.
Lomvardas S, Barnea G, Pisapia DJ, Mendelsohn M, Kirkland J, Axel R. Interchromosomal interactions and olfactory receptor choice. Cell. 2006 Jul 28;126(2):403-13.
Guan Z, Giustetto M, Lomvardas S, Kim JH, Miniaci MC, Schwartz JH, Thanos D, Kandel ER.Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure. Cell. 2002 Nov 15;111(4):483-93.
Lomvardas S, Thanos D. Modifying gene expression programs by altering core promoter chromatin architecture. Cell. 2002 Jul 26;110(2):261-71.
Lomvardas S, Thanos D. Opening chromatin. Mol Cell. 2002 Feb;9(2):209-11.
Lomvardas S, Thanos D. Nucleosome sliding via TBP DNA binding in vivo. Cell. 2001 Sep 21;106(6):685-96.
Munshi N, Agalioti T, Lomvardas S, Merika M, Chen G, Thanos D. Coordination of a transcriptional switch by HMGI(Y) acetylation. Science. 2001 Aug 10;293(5532):1133-6.
Agalioti T, Lomvardas S, Parekh B, Yie J, Maniatis T, Thanos D. Ordered recruitment of chromatin modifying and general transcription factors to the IFN-beta promoter. Cell. 2000 Nov 10;103(4):667-78.