Positions

Senior Vice President and Dean for Research
Office of the President
Baylor College of Medicine
Houston, TX, US
Interim Dean
Graduate School of Biomedical Sciences
Baylor College of Medicine
Professor
Molecular and Human Genetics
Baylor College of Medicine
Professor
Developmental Biology Program
Baylor College of Medicine
Professor
Integrative Molecular and Biomedical Sciences Program
Baylor College of Medicine
Professor
Department of Pharmacology
Baylor College of Medicine
Professor
Biochemistry and Molecular Biology
Baylor College of Medicine
Salih J. Wakil, Ph.D. Endowed Chair in the Verna & Marrs McLean Department of Biochemistry & Molecular Biology
Baylor College of Medicine
Houston, Texas, United States

Education

Post-Doctoral Fellowship at University Of California, San Diego
Developmental Biology and Genomics
PhD from Stanford University
Biochemistry
BA from University Of California, San Diego
Biochemistry and Cell Biology

Honors & Awards

Junior Faculty Research Award
Searle Scholar
Visiting Professorship
Visiting Professorship
Elected Fellow
2005 Michael E. DeBakey, M.D., Excellence in Research Award
William H. Bell Endowed Lecture
2011 Michael E. DeBakey, M.D., Excellence in Research Award
Postdoctoral Fellow

Professional Interests

  • Dictyostelium genomics
  • Cellular regulatory mechanisms that govern cell differentiation in eukaryotes
  • Dictyostelium host-pathogen interactions

Professional Statement

Dr. Kuspa's research involves the use of Dictyostelium to study problems of development and host-pathogen interactions, with an emphasis on cellular communication, cell differentiation and innate immunity. Dr. Kuspa initiated genomic studies in Dictyostelium as a postdoctoral fellow – a project that led to a collaboration with Dr. Richard Gibbs and the Human Genome Sequencing Center at BCM and culminated in the completion of the first amoebal genome sequence in 2005. With Dr. Gad Shaulsky at BCM, Dr. Kuspa also pioneered the functional analysis of the genome by developing methods for gene function discovery. Dr. Kuspa’s laboratory has also discovered novel determinants of Legionella pathogenesis involving the cleavage of Dictyostelium’s mitochondrial ribosomal rRNA and conserved proteins involved in vesicular trafficking. Recently, Dr. Kuspa's laboratory discovered an innate immune system in Dictyostelium mediated by TIR domain signaling pathways. Intriguingly, mutants in this pathway are defective in immune function during development and are compromised in their bacterial feeding behavior during vegetative growth. The apparent requirement of innate immune functions for growth on bacteria suggests that innate immunity evolved from bacterial foraging mechanisms in the progenitor of the crown group eukaryotes.

Development in a simple system

A long-term goal of Dr Kuspa’s is to define the cellular regulatory mechanisms that govern cell differentiation in eukaryotes using Dictyostelium as a model. This system can be used to provide a complete picture of the regulation of a significant biological problem: the integration of individual cells into distinct tissues with the proper form and function. 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% prespore cells and 30% 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. The similarity between Dictyostelium and human genes provides a system where the function of protein ensembles can be tested in a simple system and the results applied to understanding the function of those proteins in other systems.

Genomics

The Dictyostelium sequencing effort resulted in a highly accurate sequence of 34 million base pairs encoding 12,500 protein-coding genes. Amoebozoa such as Dictyostelium are noteworthy as representatives of one of the surviving branches of the crown group of eukaryotes. Comparisons between representatives of these branches (plants, amoebae, fungi and animals) promises to shed light not only on the nature and content of the ancestral eukaryotic genome, but on the diversity of ways in which its components have been adapted to meet the needs of complex organisms. The genome of Dictyostelium, as the first amoebozoa to be fully sequenced, should be particularly informative for these analyses. Accordingly, Dictyostelium has been designated by the NIH as one of the “model organisms”.

Functional Genomics

Functional genomics holds the promise that we can define the functions of cells and organisms by using genome-scale techniques to obtain a global view of biological systems. The Kuspa laboratory has begun large-scale functional analyses of the Dictyostelium genome, in collaboration with Gad Shaulsky and Richard Sucgang here at BCM, and Blaz Zupan at the University of Ljubljana in Slovenia. We are developing the technology that will allow us to generate and characterize mutants at a genomic scale. We have initiated a large-scale mutagenesis and “parallel phenotyping” project utilizing molecular barcodes. Recently, we have defined normal development from the viewpoint of the transcriptional profile of populations of cells using RNAseq, providing a robust “transcriptional fingerprint” of development that describes the major transitions in Dictyostelium development and defines the main cell types. This work has put us in a position to analyze mutants by comparison of their transcriptional profiles. The advantages of transcriptional profiling are now obvious since the method can be applied in a uniform way, it provides a universal phenotype and no prior knowledge of the mutated gene is required.

Selected Publications

Memberships

Association of Academic Health Centers
American Association of Medical Colleges
American Society of Microbiology
American Association for the Advancement of Science