Mark Boguski

Mark Boguski
Dr. Boguski in September 2013

Mark Boguski is the Chief Medical Officer of Liberty BioSecurity, LLC and founded the Precision Medicine Network in 2014. He is member of the U.S. National Academy of Medicine and a Fellow of both the College of American Pathologists and the American College of Medical Informatics. Dr. Boguski has served on the faculties of the U.S. National Institutes of Health, the Johns Hopkins University School of Medicine and Harvard Medical School and as an executive in the biotechnology and pharmaceutical industries. He is a former Vice President and Global Head of Genome and Protein Sciences at Novartis and a graduate of the Medical Scientist Training Program at Washington University in St. Louis. He has also written a series of books on cancer for the general public under the series title Reimagining Cancer.

Education

Boguski graduated in May 1976 from The Johns Hopkins University, in Baltimore, Maryland with a B.A. Natural Sciences. While in school, he worked as a research assistant for the Laboratory of Molecular Biology, National Cancer Institute, Baltimore Cancer Research Center from 1974-1978.

Boguski earned his M.D., Ph.D. from Washington University School of Medicine and Division of Biology and Biomedical Sciences., Medical Scientist Training Program, St. Louis, Missouri, M.D., Ph.D. (Molecular Biology), in December 1986. He was Jeff Gordon's first graduate student.

He then trained as a Resident in Anatomic Pathology from 1987-1988 in the Department of Pathology, Barnes, Children's and Jewish Hospitals, Washington University Medical Center in St. Louis, Missouri. Following this, he worked as a Medical Staff Fellow under David J. Lipman at the Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, from 1988 - 1989.

Research

Bioinformatics and computational biology

Boguski's interest in computational biology started in graduate school in the early 1980s (more than ten years before the term bioinformatics first appeared in the literature). He used and developed some of the primitive software tools of the time to study the structure, function and evolution of mammalian apolipoprotein genes.

During his Medical Staff Fellowship under David J. Lipman, Boguski shared an office with the renowned biomathematician, Stephen Altschul, with whom he co-authored several articles. In 1990, Boguski organized the first workshop on Computational Biology at the U.S. National Institutes of Health.

Boguski's subsequent work in computational biology has, over the years, involved algorithm development (e.g. Gibbs sampler, text mining), database design, development and implementation (dbEST, XREFdb, ArrayDB) and data mining, data analysis and data annotation. One database effort in particular, the database of Expressed Sequence Tags (dbEST, 1993), has enjoyed a particularly long and influential life contributing first to gene discovery and subsequently to succeeding generations of genomics applications, namely transcript mapping, design and construction of microarrays, discovery in silico of single nucleotide polymorphisms and, ultimately, analysis and annotation of the human genome.

Genes and disease

Boguski's group collaborated in the cloning and in-depth analysis of the products of a number of human disease genes including: Neurofibromatosis Type 1, Familial Adenomatous Polyposis (APC), Choroideremia, Multiple Endocrine Neoplasia Type 1 and Cerebral Cavernous Malformation. In addition, they pioneered the use of comparative genomics methods to gain broad insights into the relationships and conservation of human disease genes in experimentally-tractable model organisms including yeast, nematodes, Drosophila and rodents.

Signaling and structural biology

Sequence analysis of the NF1 gene and its GTPase-activating (GAP) domain led Boguski and his team into the ras pathway where they worked for a number of years identifying structural and functional motifs in ras signaling proteins. Notably, they elucidated the secondary structures of prenyltransferase subunits. Extensive studies were also performed on other proteins and protein families. Boguski and his team predicted that, unlike other apolipoproteins which possessed amphipathic α-helical structures, ApoD was a member of the lipocalin family composed of two orthogonal β-sheets. They also identified the first lipocalin with enzymatic activity, prostaglandin D synthase. Their threading analysis of the mouse obese gene product (leptin) predicted its unexpected structure and function as a helical cytokine, later confirmed by other groups using NMR, crystallography and cloning of the leptin receptor.

Genome and proteome research

• Comparative Genomics & Evolution - Boguski's group first coined the term comparative genomics in 1995 to describe their work on the large-scale sequence analysis of the homologs of human disease genes in model organisms and the first comparative genomics database, XREFdb. Over the next six years they studied thousands of gene sets in humans, rats, mice, Drosophila, nematodes and yeast and established the basic evolutionary parameters for interpretation of conserved protein-encoding genes in the human genome.
• Transcript Mapping - Clusters of human genes and ESTs (“UniGenes”) were utilized to construct the first comprehensive transcript map of the human genome (1996, 1998). Historically, this was the first instance of Science magazine using the World Wide Web to publish results, provide hyper-linked information resources and supplemental data sets. These maps facilitated and accelerated the positional cloning of hundreds of genes and this mapping approach was widely applied to other organisms.
• Functional Genomics - Boguski's group used human UniGenes to design and construct the first human cDNA microarray (representing 10,000 genes) and were first to provide a rigorous definition of functional genomics for the community. While on sabbatical at NHGRI, their group implemented the first relational database and analysis system, ArrayDB, for microarray data. This design was copied by numerous academic and commercial groups. Their group was also first to apply methods of statistical text-mining to the interpretation of gene expression profiles. In the 2001 Genome Issue of Nature, they immediately followed the first publication of the human genome sequence with a paper showing how to use microarray technology to experimentally annotate and correct computational gene predictions.
• Pharmacogenomics - They cloned and sequenced the pregnane X receptor (PXR) gene that encodes the key transcription factor regulating the expression of genes encoding drug and xenobiotic metabolizing enzymes. They also identified functional sequence polymorphisms in the promoters of these genes, cytochromes P450 3A (CYP3A), and studied the genotypes and corresponding molecular phenotypes in several populations differing in their drug-metabolizing abilities.
• Neurogenomics - They pioneered the application of genome-scale approaches to neurobiology with the construction of a comprehensive, 3-dimensional transcript map of the mouse brain, the Allen Brain Atlas.
• Proteomics and Knowledge Mining - At Novartis, Boguski's division was responsible for the application of proteomics technologies and computational knowledge-mining Systems Biology for drug target and biomarker discovery\

Precision medicine and comparative effectiveness research

At Harvard Medical School and Beth Israel Deaconess Medical Center, Boguski's research interests and activities included the applications of “next generation” genome sequencing technologies and network biology to the development of precision diagnostics and personalized medicine. He also worked on new approaches to drug “repurposing” involving “empowered patients,” social networking technologies, personal genotyping and health record data-mining to identify potential new uses for existing drugs. In 2009, Boguski founded the Genomic Medicine Initiative, the first training program of its kind, to prepare pathology residents to practice personalized medicine in the Genome Era. This initiative was expanded to a nationwide program supported by NIH grant 1R25CA168544-01 to Beth Israel Deaconess Medical Center and the American Society for Clinical Pathology. This program, “Training Residents in Genomics” (TRIG), is administered by a working group of the Association of Pathology Chairs (APC) and its section of residency Program Directors (APC/PRODS).

External links

• Mark Boguski’s website