Adam Kuspa, Ph.D.
Professor of Molecular and Human Genetics
Senior Vice President for Research, Baylor College of Medicine
Professor, Department of Biochemistry & Molecular Biology
Professor, Department of Pharmacology; Programs in Integrative Molecular and Biomedical Sciences and Developmental Biology
B.A., University of California, San Diego, 1983
Ph.D., Stanford University, 1989
Postdoc, University of California, San Diego, 1989-93
One long-term goal of our laboratory is to define the cellular regulatory mechanisms that govern cell differentiation in eukaryotes using Dictyostelium discoideum as a model. Dictyostelium cells normally live as solitary amoebae in the soil, consuming other microbes by phagocytosis. Upon starvation, ~50,000 cells aggregate into a mound and become an integrated multicellular organism with distinct tissue types. Each organism consists of about 70 percent prespore cells and 30 percent prestalk cells. When conditions are favorable, they form a fruiting body, the terminal developmental structure that is made up of a sorus of dormant spores held aloft on a cellular stalk. This system can be used to provide a complete picture of the regulation of a significant biological problem: The integration of individual cells into a multicellular tissue with the proper form and function.
Previously, we had studied two ABC transporters, RhT and TagA, that operate very early in development and which control aspects of initial cell differentiation. We have also characterized several components of the regulatory network that governs the growth to development transition itself: A novel putative receptor/kinase GdtB, a conserved protein kinase YakA and a conserved translational regulator PufA. These five regulators form critical links in the regulatory network that controls growth, the decision to initiate development and initial establishment of specific cell types- regulation that is common to all eukaryotes that undergo development. The function of these signaling pathways in Dictyostelium are being studied by genetic, physiological and genomic methods.
Dictyostelium Genomics: Functional genomics holds the promise that we can define most of the significant functions of cells and organisms by using genome-scale techniques to obtain a global view of biological systems. Genomics approaches will provide a unique perspective of biological regulation by completing the "parts lists" for cellular functions and by outlining connections between regulatory systems that could not be obtained by other methods. Before we can fully exploit this information we must identify the genes, understand how the genes function, and integrate this information into a comprehensive biological picture. We have recently completed the sequence of the 34 Mb genome of Dictyostelium together with the Genome Sequencing Center here. We are also planning to generate mutations in about 5,000 genes and phenotype the resulting strains using a variety of traditional and genomic methods. This work will allow us to make testable predictions of gene function and to propose regulatory networks. We are interested in those aspects of Dictyostelium biology that are common to all eukaryotic organisms, and that will be informative for defining both the function of individual genes and the organization of regulatory hierarchies that operate in development. The relative simplicity and genetic tractability of organisms such as Dictyostelium should prove to be advantageous for genomic analyses of multicellular development.
- Hirose S, Benabentos R, Ho HI, Kuspa A, Shaulsky G (2011). Self-recognition in social amoebae is mediated by allelic pairs of tiger genes. Science 333(6041): 467-70. PubMed PMID: 21700835
- Benabentos R, Hirose S, Sucgang R, Curk T, Katoh M, Ostrowski EA, Strassmann JE, Queller DC, Zupan B, Shaulsky G, Kuspa A (2009). Polymorphic members of the lag gene family mediate kin discrimination in Dictyostelium. Curr. Biol. 19(7): 567-72. PubMed PMID: 19285397
- Santorelli LA, Thompson CR, Villegas E, Svetz J, Dinh C, Parikh A, Sucgang R, Kuspa A, Strassmann JE, Queller DC, Shaulsky G (2008). Facultative cheater mutants reveal the genetic complexity of cooperation in social amoebae. Nature 451(7182): 1107-10. PubMed PMID: 18272966
- Chen G, Zhuchenko O, Kuspa A (2007). Immune-like phagocyte activity in the social amoeba. Science 317(5838): 678-81. PubMed PMID: 17673666
- Sawai S, Guan XJ, Kuspa A, Cox EC (2007). High-throughput analysis of spatio-temporal dynamics in Dictyostelium. Genome Biol. 8(7): R144. PubMed PMID: 17659086
- Eichinger L, Pachebat JA, Glockner G, Rajandream MA, Sucgang R, Berriman M, Song J, Olsen R, Szafranski K, Xu Q, Tunggal B, Kummerfeld S, Madera M, Konfortov BA, Rivero F, Bankier AT, Lehmann R, Hamlin N, Davies R, Gaudet P, Fey P, Pilcher K, Chen G, Saunders D, Sodergren E, Davis P, Kerhornou A, Nie X, Hall N, Anjard C, Hemphill L, Bason N, Farbrother P, Desany B, Just E, Morio T, Rost R, Churcher C, Cooper J, Haydock S, van Driessche N, Cronin A, Goodhead I, Muzny D, Mourier T, Pain A, Lu M, Harper D, Lindsay R, Hauser H, James K, Quiles M, Madan Babu M, Saito T, Buchrieser C, Wardroper A, Felder M, Thangavelu M, Johnson D, Knights A, Loulseged H, Mungall K, Oliver K, Price C, Quail MA, Urushihara H, Hernandez J, Rabbinowitsch E, Steffen D, Sanders M, Ma J, Kohara Y, Sharp S, Simmonds M, Spiegler S, Tivey A, Sugano S, White B, Walker D, Woodward J, Winckler T, Tanaka Y, Shaulsky G, Schleicher M, Weinstock G, Rosenthal A, Cox EC, Chisholm RL, Gibbs R, Loomis WF, Platzer M, Kay RR, Williams J, Dear PH, Noegel AA, Barrell B, Kuspa A (2005). The genome of the social amoeba Dictyostelium discoideum. Nature 435(7038): 43-57. PubMed PMID: 15875012
- Maeda M, Lu S, Shaulsky G, Miyazaki Y, Kuwayama H, Tanaka Y, Kuspa A, Loomis WF (2004). Periodic signaling controlled by an oscillatory circuit that includes protein kinases ERK2 and PKA. Science 304(5672): 875-8. PubMed PMID: 15131307
- Chen G, Shaulsky G, Kuspa A (2004). Tissue-specific G1-phase cell-cycle arrest prior to terminal differentiation in Dictyostelium. Development 131(11): 2619-30. PubMed PMID: 15128662
- Good JR, Cabral M, Sharma S, Yang J, Van Driessche N, Shaw CA, Shaulsky G, Kuspa A (2003). TagA, a putative serine protease/ABC transporter of Dictyostelium that is required for cell fate determination at the onset of development. Development 130(13): 2953-65. PubMed PMID: 12756178
- Van Driessche N, Shaw C, Katoh M, Morio T, Sucgang R, Ibarra M, Kuwayama H, Saito T, Urushihara H, Maeda M, Takeuchi I, Ochiai H, Eaton W, Tollett J, Halter J, Tanaka Y, Kuspa A, Shaulsky G (2002). A Transcriptional Profile of Multicellular Development in Dictyostelium discoideum. Development 129(7): 1543-52. PubMed PMID: 11923193
Adam Kuspa, Ph.D.
Department of Biochemistry & Molecular Biology
Baylor College of Medicine
One Baylor Plaza, MS BCM125
Houston, TX, 77030, U.S.A.