Email

gadi@bcm.edu

Positions

Professor and Director of Graduate Studies

Graduate Program in Genetics and Genomics
Baylor College of Medicine

Professor

Graduate Program in Immunology and Microbiology
Baylor College of Medicine

Professor and Vice Chair for Graduate Education Affairs

Molecular and Human Genetics
Department of Molecular and Human Genetics
Houston, Texas, United States

Addresses

BCM-Smith Medical Research Bldg (Lab)

Room: BCMS-S930
Houston, TX 77030
United States
(713) 798-8082
gadi@bcm.edu

BCM-Smith Medical Research Bldg (Office)

Room: BCMS-S930
Houston, TX 77030
United States
(713) 798-8082
gadi@bcm.edu

Education

BSc from Tel Aviv University

09/1985 - Tel Aviv, Israel

MSc from Tel Aviv University

09/1986 - Tel Aviv, Israel

PhD from Weizmann Institute of Science

05/1991 - Rehovot, Israel

Post-Doctoral Fellowship at University Of California, San Diego

06/1997 - La Jolla, California, United States

Honors & Awards

Barbara and Corbin J. Robertson, Jr. Presidential Award for Excellence In Education

Baylor College of Medicine (05/2020)

Michael E. DeBakey, M.D., Excellence in Research Award

Baylor College of Medicine (05/2011)

Michael E. DeBakey, M.D., Excellence in Research Award

Baylor College of Medicine (05/2006)

Professional Interests

• Functional Genomics and Transcriptome analysis
• The evolution of social behavior in Dictyostelium
• Allorecognition in Dictyostelium
• Developmental genetics in Dictyostelium

Professional Statement

Functional genomics: In the past we have used microarrays to discover gene function in development, de-differentiation, spore germination, drug resistance, and chemotaxis (e.g. Booth et al., 2005; Van Driessche et al., 2007). We also showed that the transcriptome is a good phenotyping tool for discovering epistatic relationships between genes in the cAMP-dependent Protein Kinase regulatory pathway (Van Driessche et al., 2005). Later, we adapted the use of RNA-seq to Dictyostelium and began to use it as our main platform for transcriptional profiling. We compared the developmental transcriptomes of D. discoideum and D. purpureum, two Dictyostelium species whose genomes are as different from each other as the genomes of humans and jawed fish, but whose developmental morphologies are very similar. We found vast similarities between the two transcriptomes (Parikh et al., 2010). We have analyzed many mutants in our lab and in collaboration with others (Cai et al., 2014), and we have developed a system for analysis of transcription factors with RNA-seq and ChIP-seq (Santhanam et al., 2015). Using frequent sampling and RNA-seq we found complex regulation of transcriptional activity during D. discoideum development (Rosengarten et al., 2015) and we described the long-non-coding transcriptome as well (Rosengarten et al., 2017). All of our transcriptome data are available for interactive exploration on dictyExpress. We are currently working on analyzing the major transcriptional transitions that characterize D. discoideum development using the RNA-seq profiles of 20 mutant strains.

We have developed several new tools for exploration of the D. discoideum genome. The most recent ones include a deep coverage genomic DNA library (Rosengarten et al., 2015) and a method for gene discovery by chemical mutagenesis at low level and whole-genome sequencing to identify mutations (Li et al., 2016). We also adapted the GoldenBraid system as a synthetic biology tool for D. discoideum (Kundert et al. 2020) and deposited dozens of new strains and vectors in the Dicty Stock Center.

The evolution of social behavior in Dictyostelium: Social organisms must deal with cheaters - individuals that reap the benefits of sociality without paying the costs. In Dictyostelium, some cells sacrifice themselves and benefit other cells that may be genetically different, providing a fertile ground for cheating. In collaboration with Drs. Strassmann, Queller and Kuspa, we found over 100 genes that participate in social interactions (Santorelli et al., 2008) and used genetic tools to characterize mechanisms that determine social interactions and test how cooperators resist cheating (Khare and Shaulsky, 2006; Khare et al., 2009; Khare and Shaulsky, 2010).

Allorecognition in Dictyostelium: Multicellular organisms can distinguish self from non-self through various mechanisms. We have found that D. discoideum cells preferentially cooperate with their relatives (Ostrowski et al., 2008), possibly reducing their exposure to strains that can cheat on them. We are now investigating the molecular mechanisms that underlie kin discrimination. We found two cell-cell adhesion genes, tgrB1 and tgrC1, that are highly polymorphic in natural populations and are required for allorecognition (Benabentos et al., 2009). Gene replacement experiments have shown that the sequence polymorphism in these genes is sufficient to explain allorecognition in this system (Hirose et al., 2011). This kin-recognition system protects cooperators against cheaters (Ho et al., 2013) and it is temporally regulated, which allows it to evolve despite its essential role in development (Ho et al., 2015). We are investigating the cellular and genetic mechanisms that regulate allorecognition under the hypothesis that the TgrB1 and TgrC1 proteins function as a ligand-receptor pair (Hirose et al., 2017), which is at the top of a signal transduction mechanism that regulates development and allorecognition. Some of these signal transduction genes were found using a genetic suppressor screen with chemical mutagenesis and whole-genome sequencing (Li et al., 2016) and we are continuing the characterization and identification of additional signaling elements.

Data Mining: We are collaborating with Dr. Blaz Zupan and his group at the University of Ljubljana in Slovenia to develop new concepts in genetic analysis. Previously we have developed a tool that performs automated epistasis analysis, GenePath (Demsar, 2001). We developed a gene function prediction system that relies on compressive data fusion and chaining and demonstrated its utility in predicting the function of bacterial-recognition genes in D. discoideum (Zitnik et al., 2015). We also developed dictyExpress, a web tool that can access and analyze our transcriptional profiling data (Stajdohar et al., 2017). Two of our recent collaborative projects include scOrange, a tool for analyzing single cell RNA-seq data (Stražar et al., 2019) and an image analysis platform that utilizes deep models in a visual programming environment (Godec et al., 2019). Our current collaboration with the Zupan group is focused on RNA-seq data mining.

Websites

Selected Publications

• Ho HI, Hirose S, Kuspa A, Shaulsky G "Kin Recognition Protects Cooperators against Cheaters.." Curr. Biol.. 2013 23 (16): 1590-1595. Pubmed PMID: 23910661
• Khare A, Santorelli LA, Strassmann JE, Queller DC, Kuspa A, Shaulsky G "Cheater-resistance is not futile.." Nature. 2009 October 15; 461 (7266): 980-2. Pubmed PMID: 19794414
• Santorelli LA, Thompson CR, Villegas E, Svetz J, Dinh C, Parikh A, Sucgang R, Kuspa A, Strassmann JE, Queller DC, Shaulsky G "Facultative cheater mutants reveal the genetic complexity of cooperation in social amoebae.." Nature. 2008 February 28; 451 (7182): 1107-10. Pubmed PMID: 18272966
• Benabentos R, Hirose S, Sucgang R, Curk T, Katoh M, Ostrowski EA, Strassmann JE, Queller DC, Zupan B, Shaulsky G, Kuspa A "Polymorphic members of the lag gene family mediate kin discrimination in Dictyostelium.." Curr. Biol.. 2009 April 14; 19 (7): 567-72. Pubmed PMID: 19285397