James Freyer - candidate for Biological Councilor

After receiving a BA in Physics from LaSalle College (1976), I received my MS (1978) and Ph.D. (1982) degrees in Biophysics from the University of Rochester, working under the mentorship of Dr. Robert Sutherland. My Ph.D. project involved the use of the multicellular tumor spheroid, an in vitro model of the tumor microenvironment, to investigate the regulation of cellular proliferation and physiology. I went to the Life Sciences Division of the Los Alamos National Laboratory in 1982 as a Director’s Office Postdoctoral Fellow, working in applications of flow cytometry to radiation biology. I became a Technical Staff Member at Los Alamos in 1984, the year that I received my first NIH grant for a project on the regulation of proliferation in spheroids. I have maintained essentially continuous NIH funding since that time, as well as having been awarded grants from DOE, NSF, LANL internal funds, the University of California and the US-Israeli Binational Foundation. In 1998 I was appointed Adjunct Professor in the Department of Cell Biology & Physiology at the University of New Mexico. In 2003 I was appointed a Full Member of the UNM Cancer Research and Treatment Center. In 2005 I was selected as the Director and PI of the National Flow Cytometry Resource. Last year I was selected as the Group Leader of the Advanced Measurement Science Group in the Biosciences Division at LANL. I have ~60 peer-reviewed publications, five review chapters and a dozen or so proceeding papers covering a wide range of scientific areas and techniques, including cell biology, cellular physiology, radiation biology, NMR imaging and spectroscopy, molecular biology, elastic and Raman scatter spectroscopy and mathematical modeling, in addition to flow cytometry. I believe that my work has had an impact in a variety of areas, as evidenced by over 2,000 citations to date. I have extensive experience as a grant application reviewer, primarily for NIH but for a number of other agencies as well. I have reviewed papers for a wide range of journals (from Cancer Research to Physics Review E), including many for Cytometry. I am a past Associate Editor of Radiation Research and current Associate Editor of the International Journal of Radiation Oncology, Biology and Physics. Finally, I have maintained an active role in student mentorship through supervising a dozen PostDocs and more than 50 graduate and undergraduate students in a variety of degree-based and educational outreach programs. I am particularly proud of having won an Outstanding Mentor Award in 2002 for my work as Co-Director of an NSF-funded Research Experiences for Undergraduates program.

I was first introduced to flow cytometry in 1978 in the laboratory of Dr. Paul Horan at the University of Rochester. I remember collecting data on one of the first Coulter TPS-2 instruments by taking Polaroid photographs of single histograms, then entering the individual channel contents into a computer by hand to do cell cycle analysis. Since that time I have applied a variety of flow cytometric analysis methods (cell cycle and proliferation, cell surface labeling, light scatter, biochemical composition, mitochondrial analysis, ratiometric analysis, coculture separation) and sorting techniques (volume based sorting for clonogenicity assays, large particle sorting, multicolor sorting of heterogeneous cell populations). Doing a PostDoc at Los Alamos introduced me to the National Flow Cytometry Resource (NFCR) and I am privileged to have been involved with this incredible flow cytometry development and application team since that time (~25 years). Perhaps due to being surrounded by technology development ‘geeks’, I have an instrument development bent: I have built several flow cytometers from the ground up and modified several others. However, my flow cytometry development work has always been directed at improving the instrumentation for the purpose of accomplishing a specific research goal, as is evidenced from my publication record. For example, we developed a volume-based sorter for plating a precise number of cells in dishes for measuring low-dose radiation effects and applied this instrument to several radiobiology studies until the flow technique was supplanted by even more precise image-based methods.

Current Interests

I am currently involved in four somewhat overlapping areas of research. I continue my longstanding interest in pursuing an improved basic understanding of the tumor microenvironment using in vitro multicellular models. Our current funding focuses on molecular mechanisms of cell cycle regulation and the application of metabolomic techniques to tumor cell metabolism. For the past ten years I have been intimately involved with a program, lead by Dr. Judith Mourant, to develop elastic light scattering and Raman spectroscopy techniques for noninvasive cancer diagnosis. This program has now reached the stage of clinical trials of a fiberoptic diagnostic probe for cervical cancer. I continue a small effort in developing and applying mathematical models of tumor growth and development in collaboration with Dr. Yi Jiang, a theoretical biologist. Finally, in 2005 I was chosen as the Director of the NFCR and was faced with the challenge of securing a sixth consecutive competitive renewal of this Biomedical Technology Research Resource from NIH. Fortunately for me, the Los Alamos team continues to be truly outstanding, and we were successful in renewing the NFCR grant for another fiveyear period starting in 2007. In addition to directing and coordinating the collaborations, service projects, training and dissemination activities of the NFCR, I am also PI on an R&D project focused on developing an integrated phase-resolved, full spectral resolution flow cytometer.

Leadership Experience

I have fairly extensive leadership and management experience that I believe will be valuable in my role as Councilor for ISAC. I served for 20 years on the LANL Institutional Biosafety Committee, including 12 years as Chair. Starting in 1990, I have extensive experience with all aspects of the NIH grant review process, having served on three different Study Sections, numerous site visits and many special panels up to the present. From 2000-2001, I served as the Acting Division Director for the Bioscience Division, overseeing the research activities and personnel management of ~300 staff members, technicians, postdocs, students and administrators. In 2005 I became the NFCR Director, which involves oversight of ~20 team members and coordination of the five components of a fairly complex, multi-million dollar P41 grant. Notably, this involves extensive collaboration and service programs as well as very active efforts in training and research dissemination. I have been involved with the Annual Course in Flow Cytometry since its inception 30 years ago, and was responsible for organizing and running the (highly successful!) courses at Los Alamos in 2005 and 2007. Following a reorganization of the Bioscience Division in 2006, I was chosen as the Group Leader of the new Advanced Measurement Science Group (~60 people), which is comprised of three teams: Signature, Assay and Ligand Development; Optical Spectroscopy and Instrumentation; and Structural Biology. My major role here is personnel management and new project development. I have been involved with numerous committees at LANL and elsewhere, generally focused on the postdoctoral and student programs. I am proud to be recognized at LANL as a scientific and personal mentor to all levels of personnel, from other technical staff members to office administrators. Finally, I have been a member of the National Ski Patrol for 20 years and a high school soccer referee for 10 years, both positions that require an interesting set of leadership and management skills.

Campaign Statement

I believe that my broad research background combined with my long fascination with flow cytometry make me well suited to take on the role of Biological Councilor for ISAC. My view is that advances in flow cytometry instrumentation and data analysis have always outpaced the actual research applications. This trend continues, and is even accelerating, today, with the explosive growth in multiplexed, multicolor analysis, increasingly sophisticated sorting technologies and advances in digital data collection and processing. Being a techno-geek myself, I think this is fantastic, but it is important to keep this technology grounded in real, beneficial applications to the biomedical sciences. Importantly, NIH is coming around to the idea of pursuing technological solutions for improving the biomedical research enterprise. Read the “high-throughput, high information content” and “research teams of the future” sections of the NIH Roadmap and I believe you will find a description of precisely what flow cytometry brings to this table. I see my role as Biological Councilor to be the fostering of biomedical applications of analytical cytometry to address real-world problems in disease diagnosis and treatment. This role is very similar to my job as Director of the NFCR, where I have had some recent success in developing and disseminating applications of our new technologies. Although I have no preconceived agenda, there are several goals for ISAC that I believe I am very well suited to champion and work towards.

• Increasing the involvement of early career scientists and students in ISAC and analytical cytometry in general. Everyone has this as a goal, understandably, but I believe it needs to be explicitly emphasized in all aspects of Society operations (meeting location, timing, program and organization; outreach and training efforts; membership recruitment and retention; and scholarship/award programs).
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• Improving the visibility of analytical cytology in the general biomedical community, through educational and training outreach efforts and partnerships with other scientific societies.
• Better integrating the ‘instrumentalists’ and the ‘experimentalists’, for lack of a better way to put it, through combined technical/scientific sessions addressing a research need (e.g. high-throughput screening or stem cell sorting) and sponsorship of smaller, focused satellite meetings.
• Strengthen the NIH portfolio in analytical cytometry through better dissemination of technical and scientific advances, targeted participation of NIH managers in ISAC activities, and improved grantsmanship of ISAC scientists (particularly young investigators) through a grant writing workshop.