The K07 Career Development Award will enable Dr. Donald Lamkin to achieve his career goal of becoming an independent investigator and future leader in translational biobehavioral cancer research. This proposal builds upon Dr. Lamkin's previous training in basic laboratory science, utilizing animal models of cancer and behavior to address biobehavioral questions in the area of cancer control. Training: The award will facilitate training specifically in (1) learning the cancer treatment regimens and research protocols that characterize clinical investigation at a comprehensive cancer center, (2) mastering functional genomics strategies and related technologies to study global gene expression in distinct cell populations within tumors, and (3) learning fluorescence microscopy and laser capture microdissection to visualize and retrieve cells in tumor microenvironments. The proposed training will allow Dr. Lamkin to acquire new skills that are essential for a translational scientit who wants to work at the boundaries of basic laboratory discovery and clinical investigation. Mentors & Collaborators: Dr. Patricia Ganz, a medical oncologist and Director of Cancer Prevention and Control Research at the UCLA Jonsson Comprehensive Cancer Center; Dr. Julie Bower, a clinical psychologist with expertise in immune, endocrine, and psychological factors in breast cancer patients and survivors; Dr. Steve Cole, a translational scientist and Director of the Social Genomics Core Laboratory at UCLA; Dr. Shimon Weiss, Director of the Advanced Light Microscopy-Spectroscopy Core Laboratory at UCLA; and Dr. Erica Sloan, a cancer biologist with expertise in preclinical models of breast cancer and neural- mediated metastasis. Research Plan: The Research Plan for this project builds upon two emerging findings in breast cancer research: First, preclinical evidence indicates that chronic stress induces a high buildup of alternatively activated (M2) vs. classically activated (M1) macrophages in tumors. This is significant because macrophages with M2 properties are increasingly becoming associated with poor outcomes in breast cancer. Thus, Aim 1 will examine the relationship between stress-related psychosocial factors and M2-related gene expression by macrophages in tumors of breast cancer patients. Second, preclinical research suggests that M2 macrophage buildup does not derive from blood stream monocytes that infiltrate the tumor but instead results from enhanced proliferation of macrophages that are already residing in the tumor microenvironment. Establishing such a finding in humans would challenge current ideas about how to target macrophages in cancer and open up new therapeutic opportunities. Thus, Aim 2 will investigate the extent to which M2 macrophages in primary tumor of breast cancer patients are locally established proliferating tissue macrophages.
Aim 3 will experimentally determine whether chronic stress increases M2 macrophage proliferation in mammary tumors of mice. This plan will facilitate Dr. Lamkin's career training objectives and position him for a future R01 submission.
Recent discoveries in basic laboratory science suggest that stress hormones can increase the presence of a certain type of immune cell in breast tumors. These immune cells are known as macrophages and are increasingly becoming associated with poor outcomes in breast cancer patients, because they can facilitate deadly spread of the tumor to other parts of the body. Basic laboratory research also suggests these macrophages can accumulate in the tumor through pathways that are not commonly thought of as potential targets for therapy in humans. Thus, this research project proposes a 'bench to beside' investigation to determine whether these basic findings hold in breast cancer patients. The results will tell us to what extent psychosocial stress-related factors may facilitate progression of breast cancer and will also give us further insight into how to target macrophage cells in the tumor.
| Chun, K; Capitanio, J P; Lamkin, D M et al. (2017) Social regulation of the lymph node transcriptome in rhesus macaques (Macaca mulatta). Psychoneuroendocrinology 76:107-113 |
| Lamkin, Donald M; Ho, Hsin-Yun; Ong, Tiffany H et al. (2016) ?-Adrenergic-stimulated macrophages: Comprehensive localization in the M1-M2 spectrum. Brain Behav Immun 57:338-346 |
