Modeling Cancer Progression in Mice
Cancer cells often develop through a progressive sequence: from normal cells, to pre-cancerous, to transformed, then to local metastasis, followed by metastatic disease, and finally aggressive metastatic disease.
Researchers have created a series of mouse cell lines that mimic this stepwise progression. These sequentially developed cell lines allow scientists to study the molecular changes, behaviors, and treatment responses that occur at each stage of cancer development. This model provides valuable insights into how cancer evolves and spreads, helping guide strategies for early detection, prevention, and therapy.
Durwood Barber Ray, Ph.D., Gerald A Merrill, Ph.D., Frederic J Brenner, Ph.D., Laurie S Lytle, Tan Lam, et al “T24 HRAS Transformed NIH/3T3 Mouse Cells (GhrasT-NIH/3T3) in Serial Tumorigenic Passages Give Rise to Increasingly Aggressive Tumorigenic Cell Lines T1-A and T2-A and Metastatic Cell Lines T3-HA and T4-PA.” Experimental Cell Research 340, 1-11, 2016.
Ray, D. B., Lam, T. M. and Jones, D. H. "Lactate Formation and Mitochondrial DNA Structure in Mouse Cells Progressing to Malignancy." Federation Proceedings, 48 (1990) 763A.
Medical Genetics Research – Fragile X Syndrome
After completing my undergraduate studies, I worked full-time at Children’s Medical Center in Tulsa, where I studied Fragile X Syndrome. Our research focused on mapping the FRAXA chromosome using six polymorphic loci: DXS369, DXS297, DXS296, DXS304, IDS, and DXS374.
We conducted genetic linkage analysis on 32 Fragile X [fra(X)] families using 12 polymorphic loci, including these new markers. By combining cytogenetic and molecular data in two-point linkage analysis, we were able to estimate lod scores and carrier probabilities for potential carriers.
The introduction of these six new marker loci significantly changed the carrier risk estimates for members of 7 of the 32 families compared to previous estimates based on less closely linked probes available before 1989. I was a co-author on this study, which was published in the American Journal of Medical Genetics, Volume 43, pages 312–319 (1992).
Carpenter, Nancy J., Swart-Boyd, Jennifer, Prichard, Jane K., Lam, Tan M. "Linkage and risk assessment in fragile X families using new DNA probes at Xq27." American Journal of Medical Genetics 43, 312-319, 1992.
Immunology and Virology Research
As a graduate student, I completed three laboratory rotations focused on: Studying viral enhancers in leukemia specificity. Investigating cholesterol acyltransferase (ACAT). Examining gamma interferon (IFN-γ) regulation of MHC class I gene expression I was a co-author on the study of gamma interferon, published in Cellular Immunology (150:90–100, 1993).
For my thesis, I focused on epitope variation in cytotoxic T lymphocyte (CTL)-resistant murine leukemia viruses, identifying minor and major epitopes. This research required me to analyze experimental results independently, design follow-up experiments, modify techniques, and troubleshoot technical problems.
My work led to two publications:
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Viral Immunology 7:51–59, 1994
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Journal of General Virology 76:635–641, 1995
Through these experiences, I developed strong skills in molecular immunology, virology, experimental design, and problem-solving in complex laboratory research.
Hillary D. White, Douglas A. Roeder, Tan M. Lam, and William R. Green. "Major and Minor Kb-Restricted Epitopes Encoded by the Endogenous Ecotropic Murine Leukemia Virus AKR623 That Are Recognized by Anti-AKR/Gross Virus CTL." Viral Immunology 7, 51-59, 1994.
Publications:
Tan M. Lam, Michael A. Coppola, Rendall R. Strawbridge and William R. Green. "Recognition of Endogenous Ecotropic Murine Leukemia Viruses by Anti-AKR/Gross Virus CTL." J. of General Virology 76, 635-641, 1995.
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