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Research in Cancer Diagnostics at Oncotech
David Smith, Ph.D.
A Science Advisory Board Member Since 2002



Smith manning the barbeque pit at a company picnic.




David Smith, Ph.D, is a Principal Investigator for the biotechnology company Oncotech, US, where he focuses primarily on cancer diagnostics. Smith received his Ph.D. from Texas A&M University, in Biochemistry and Biophysics. After a post-doctoral fellowship at UCLA, he accepted a position at ICN Pharmaceuticals in 2001. ICN Pharmaceuticals went through a series of acquisitions and mergers during the next few years, and he was recruited to Oncotech in 2005. Smith received the Kern Aspen Lipid Conference Young Investigator Award (August 14, 1999), the American Heart Association Postdoctoral Fellowship Award (July 1, 2000 - June 30, 2001) and is a member of the American Association for Cancer Research.






Academic Background


I obtained my bachelors degree from the University of Texas at Austin back in the day when a Biochemistry degree fell under the auspices of “Art” rather than “Science”. Either I’m really old or the UT system is recalcitrant to change (or maybe both?!). I then became traitor to UT and moved to Texas A&M (UT’s rival) where I obtained my Ph.D. in Biochemistry and Biophysics in the lab of Dr. Ry Young.


My Ph.D. thesis centered on an amazing group of proteins known as “holins”, elicited by bacteriophages. These are integral membrane proteins that have two functions: 1) they are responsible for destruction of a viable bacterial cell membrane and 2) at a predetermined time dictated by the amino acid sequence of the holin protein. The culmination of my thesis research was (by standing on others’ shoulders) the successful overexpression of these lethal proteins while maintaining function and reconstitution of these holes in situ.


Professional Background


After obtaining my Ph.D., I switched fields and accepted a post-doctoral fellowship at UCLA, more specifically at the VA Research unit in the Lipid Research Lab, directed by Dr. Michael Schotz. I worked directly with Dr. Howard Wong, a PI on the NIH P01 Grant, and Judy Nikazy to expand research to dissect the functional roles of domains and subdomains of lipoprotein lipase and other lipase family members. During the second year of the post-doc, I was awarded a fellowship from the American Heart Association.


After two and a half years in Howard’s lab, I accepted a position at ICN Pharmaceuticals where an extensive effort to initiate a new phase of research was well under way in 2001. I worked for Dr. Jim Wu in the Biochemistry group to develop and implement assays to screen the in-house library of small molecules against viral and oncological targets. During my tenure at ICN, the R&D group was spun off as an IPO named Ribapharm. ICN later re-acquired Ribapharm and subsequently underwent a “re-branding” of the company and changed the company name to Valeant Pharmaceuticals. The R&D group was later sold to Ardea Biosciences, where the potent SAR compound series that we identified and developed against the signal transduction pathway kinase MEK1 has now entered clinical trials.


In 2005 I was recruited to Oncotech by Dr. Bill Ricketts, a former colleague at ICN, to focus research efforts on personalized medicine (specifically cancer diagnostics). Oncotech was recently acquired by Exiqon and we are now re-tooling to adopt the parent company’s microRNA platform and technology. The marriage between Oncotech with its tumor bank, associated drug response data, and research capabilities and Exiqon’s phenomenal microRNA and LNA (Linked Nucleic Acid) platform, IP and technology, is a union that should drive the new company to the absolute forefront of cancer diagnostics.


Describe your research at Oncotech.


My current title at Oncotech is Principal Research Scientist and my current research interests center on the development of novel diagnostics that will enable us to identify and employ genomic markers that will empower medical oncologists with information and the ability to prescribe chemotherapy in a patient-specific manner. I am very practical minded and goal oriented. If a new kit or device or modification of a kit or device is called for to facilitate achieving a goal, then I will pursue that as a means to an end. For example, we’ve modified a commercial assay kit to meet our needs and then co-published the modification in the kit maker’s periodical. We are also currently collaborating to develop new devices to improve isolation of nucleic acid from various organisms. We actively support and promote such interactions between suppliers and our own research--it is frequently beneficial for both parties.


What initiated your interest in science research?


I have been keenly interested in science and basic type research for as long as I can remember. I was introduced to real research while attending UT Austin. I was a microbiology major and discovered that my wife’s technician position in a biochemistry lab afforded me a really nice quiet conference room for studying. At one point her boss, Dr. Joann Ravel, noted that I spent considerable time in their conference room and asked me what my major was. After indicating microbiology, she simply asked me what I intended to do with a micro degree. All I knew was that I enjoyed the coursework immensely and wanted a career in the field. She sat down and “informed” me that biochemistry would be a superior foundation for a research career. Then she offered me a student worker position in her lab. I poured protein gels and chromatography columns, helped purify proteins and run ELISAs. I was hooked. I switched majors soon after and have never looked back. Throughout the course of my education and training I have enjoyed the camaraderie of many gifted scientists and teachers who have influenced my course in research. There’s not enough space or time here to list those individually, but each has had a role in my motivation to pursue basic research. But the driving force is my innate curiosity to know just how things work.


Has your career progressed as expected?


That’s a tough question. I’d have to answer “yes and no.” Yes, in that I’m still in science and conducting basic research. I’d have to answer ‘no’ because in the beginning I had intentions of tackling the biochemistry behind alcohol addiction. I can’t say exactly why that field attracted me--no one in my family or within my circle of friends growing up that I knew had an addiction that I was aware of. Somewhere along the way during my undergrad education I read a paper about alcoholism and adrenergic receptors. It fascinated me that a membrane-tethered protein could effectively and literally play the role of a mechanical switch.


I’m sure it was this concept of membrane proteins regulating viral lysis that attracted me to Dr. Ry Young’s lab. (Many of the students at A&M thought I was crazy to join Ry’s lab--he had a notorious reputation for being ‘difficult’. I learned that rigorous was a better description; Ry was a phenomenal mentor.)


At a conference once someone referred to my success in the field of lysis as “working on dinosaurs”. I couldn’t help but smile at the irony. Everything we know, everything he knew, was literally based on the paradigm of research of phage biology. Practically everything. Yes, it’s difficult to obtain federal funding for projects focusing on phage research--the application of that knowledge has to be practical and must relate directly to some ‘eukaryoticly’ important facet of acceptable research. Oh, I suppose you could pitch lysis research as important in, say, research focused on anti-bioterrorism in the area of controlling anthrax cultures or some such. But it seems a shame to me to think that we’ve “moved on” from phage research assuming we’ve learned most of what there is to know. In all honesty, I think we’ve barely scratched the surface. Nevertheless, I do not regret moving on and changing fields. I still keep in touch with Dr. Young and follow the holin story closely, but I thoroughly enjoy the work I do now and find it very rewarding to know that cancer patients have a brighter future. Although punching holes in bacteria was cool, it didn’t give me that warm fuzzy feeling.


What would you like to achieve with your research in the future?


My current career goal is to meet the objective of the new mother company, Exiqon, and bring to market new diagnostics to aid cancer patients. I think our goals are well aligned in the details of the research. We are adopting the Exiqon platform of microRNA based research. The recent literature has come alive with indications of microRNA signatures associated with cancer. Our goal is to identify signatures that correlate with drug resistance and develop new diagnostic tests that will allow physicians to avoid prescribing a therapy with horrible side effects to an individual for whom it will have no significant benefit and who is already suffering. I think such microRNA signatures could also be easily employed to drive the development of new therapies in a pre-clinical arena. The possibilities are very real and very tractable.


What are your hobbites and interests?


First and foremost I am a family man. My family will ALWAYS come first! I love to spend time with my kids (3 boys and 1 girl). We’re actively involved in The Boy Scouts of America; I strongly endorse the values that program instills in the youth. All of my kids have played or are currently playing European football (a.k.a. soccer) so I’ve spent a fair amount of time refereeing AYSO soccer games. I think the amount of time we invest personally in our youth will pay great dividends to our future society. I’m a staunch advocate of the phrase, ‘Today’s youth are tomorrow’s leaders.’


My hobbies are much like my scientific career. I enjoy figuring out how things work. And I enjoy serving others and sharing these experiences with others. Some years ago I learned that a person could build a telescope from scratch with little or no equipment. Having been an avid stargazer as a kid under the relatively dark skies of East Texas I latched on to the idea and have since built my own 16 inch lightweight Dobsonian reflecting telescope. The building and modification of it is documented on my website. There are few things more enjoyable than observing incredible nebula and planetary detail with an instrument that I built with my own hands. I like to set up out in the driveway and share the views with the neighbors.


I also love to cook. Being a native Texan and having been brought up experiencing southern barbecue on a regular basis, I was surprised to find there’s a dearth of true smoked BBQ here in Southern California. Several years ago my dad welded a BBQ pit for me, loaded it in his pickup truck with a fork lift, and drove it out here. Over the course of 16 hours I can cook about 200 pounds of meat. I’ve become quite popular at the family reunions and get-togethers! Maybe I should reconsider that career path question?






To discuss cancer diagnostics and other topics with fellow Science Advisory Board members, please visit our community forum.


Web Links


Exiqon


Oncotech


David Smith's Personal Home Page


Patents & Publications


Colloids and Surfaces B: Biointerfaces 58 (2007) 44–51, A novel, compact disk-like centrifugal microfluidics system for cell lysis and sample homogenization, Horacio Kido, Miodrag Micic, David Smith, Jim Zoval, Jim Norton, and Marc Madou.


CellTiter-Glo® Luminescent Cell Viability Assay: Application for Viability Studies of Cells Grown in Agarose. Promega Cell Notes, January 2007 Issue 17, p16 Applications of Luciferase Reporter Assays.


Oncotech Patent:
Reagents and Methods for Predicting Drug Resistance. Inventors: Christopher Kerfoot, William A. Ricketts, and David L. Smith (filed for Oncotech, Inc. December 2, 2005)


J. Bacteriol., 1998, 180 (16), 4199-4211, Oligohistidine tag mutagenesis of the Lambda holin gene, David L. Smith and Ry Young.


J. Bacteriol., 1998, 180 (9), 2531-2540, Purification and biochemical characterization of the lambda holin, David L. Smith, Douglas K. Struck, J. Martin Scholtz, and Ry Young.



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