For the past 20 years I have studied the biology of the urochordate Botryllus schlosseri and contributed to its development as a model organism for the study of stem cell biology, immunology and evolution. As a postdoctoral fellow in Irv Weissman’s lab. at Stanford, I identified and isolated the first adult stem cell (Cell Stem Cell, 2008) and the first germline stem cell niche in B. schlosseri (Dev. Cell, 2013). I also discovered that B. schlosseri exhibits an alternative regeneration pathway whereby whole body regeneration occurs from the vasculature alone: a process in which a normal colony of individuals is regenerated through multiple generations of abnormal intermediate forms that gradually converge into an individual with normal physiology and morphology (FASEB J., 2007). Since 2010, I have been directing and conducting the B. schlosseri genome project, a project that has involved 19 scientists in bioinformatics and molecular and cell biology from Irv Weissman’s and Stephen Quake’s labs and several international laboratories. Using our novel method for high-throughput sequencing of repeat-rich genomes (called LRseq; acquired by Illumina), we sequenced and assembled the 580-Mbp of the B. schlosseri genome. The B. schlosseri genome revealed critical events underlying the early evolution of vertebrates, including the first known appearance of genes related to hematopoiesis, cardiac, optic and auditory development (Elife, 2013). Using this newly sequenced B. schlosseri genome, we looked carefully into a single polymorphic gene locus that governs fusion/rejection outcomes in B. schlosseri colonies. This locus, called Fu/HC for fusion/histocompatibility, encodes multiple co-dominant alleles in natural populations, and progeny from crosses between histocompatible colonies are known to segregate in a manner consistent with a monogenetic trait. Using genetically Fu/HC defined lines, whole-transcriptome sequencing of 23 colonies, and a novel genomics approach, we identified BHF, the gene that encodes self and determines “graft” outcomes in this organism. Our genome-wide study revealed the first fusion-rejection system understood to the point where one can reliably predict, based on a single gene, the outcome of histocompatibility reactions. These findings establish an experimentally tractable platform for advancing the science of allorecognition (Science, 2013). Using the resources and tools we and others developed we continue our studies on BHF and the evolution of blood borne immune system.
Current Role at Stanford
Advising and Mentoring
(1) 831-224-2187 Postdoctoral Fellow, Weissman Lab.
Mark Alec Kowarsky
Doctoral program physics, Quake Lab.
Pre Major Advisees
Ratteray, Alida Nicole
1 (603) 921-7328Undergrad, ENGR-BS, Junior
Philp, Charlotte Victoria
1 (650) 391-3140Undergrad, BIOE-BS, Junior
Stevens, Lydia Rose
(805) 440-9115Undergrad, UNDCL-B, Sophomore
Lim, Joseph Patrick
(501) 305-1504Undergrad, UNDCL-B, Sophomore
Kumarasinghe, Raveen Lashlen
(510) 766-5999Undergrad, UNDCL-B, Sophomore
Education & Certifications
Postdoctoral Fellow, Stanford University, Stanford, California, Stem Cell Biology (2006)
Ph.D, Technion, Israel institute of technology, Haifa, Cell Biology (2001)
M.Sc, Tel-Aviv University, Tel-Aviv, Israel, Zoology (1995)
B.Sc, The Hebrew University of Jerusalem, Israel, Animal science (1991)
Ayelet Voskoboynik; Dmitry Pushkarev, Stephen Quake. "United States Patent 61/532,882; International application No. PCT/US2012/054461 Methods for obtaining a sequence. US 61/532,882, filed September 9, 2011(Pending); International application No. PCT/US2012/054461, filled September 10, 2012 (Pending); United Kingdom patent application 1216076.8 filed September 10, 2012 (Pending)"