The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

 Melissa B. Aldrich, Ph.D.

Melissa B. Aldrich, Ph.D.

Assistant Professor, Center for Molecular Imaging

Melissa.B.Aldrich@uth.tmc.edu

713-500-3565

Dr. Aldrich received her B.A. in Biochemistry from the University of Texas-Austin, M.B.A. from the University of Houston, and Ph.D. in Immunology from the University of Texas Graduate School of Biomedical Sciences in Houston, focusing on severe combined immune deficiency.  Her postdoctoral training at Baylor College of Medicine entailed development of cancer dendritic cell and DNA vaccine strategies, including study of regulatory T cell and memory T cell responses.  Dr. Aldrich’s interests lie in investigating immune factors that influence lymphatic dysfunction and in translating lymphatic imaging technology to the clinic.

Dr. Aldrich brings a combination of expertise in translational science and immunology to lead the program of lymphatic imaging, the circulatory system which is critical to immune surveillance and response.  NIRF imaging promises to deliver high-resolution, low-cost images of lymphatic vessel architecture and pumping.  In disease states such as lymphedema, manifested by severe limb swelling, NIRF imaging can provide information for diagnosis and evaluation of treatment efficacy.  As part of a translation team, Dr. Aldrich has conducted clinical measurements that prove the usefulness of NIRF imaging to investigate lymphatic vessel architecture and function in health and disease.  Her study of NIRF images of breast cancer-related lymphedema arms revealed that the severity of the disease worsens over time not only in the “affected” arms (that received surgical and/or radiological treatment associated with the side of breast cancer treatment), but also in the contralateral (“unaffected”) arms.  This work added evidence to other studies suggesting that lymphedema is a systemic, not just local, disease.  Dr. Aldrich will lead a new five-year NIH-funded prospective study of breast cancer patients who are at high risk of developing lymphedema, investigating immunological changes that may contribute to lymphedema.  Dr. Aldrich has also worked in NIRF imaging studies of primary, or genetic, lymphedema and rare fat-associated genetic disorders with lymphatic abnormalities.  Dr. Aldrich recently conducted a study of pneumatic compression therapy (PCT) for lymphedema, and produced visual “proof” that this modality enables lymph movement in grades I, II, and III lymphedema patients.  The Centers for Medicare/Medicaid and other major medical insurers have previously denied reimbursement for this therapy, pending proof of efficacy.  These study results could enable provision of PCT for the millions of lymphedema patients in the U.S.

“Translation” is a much-used term in research that stresses the importance of research that is relevant to medical practice.  Truly crossing the “bench to bedside” chasm, however, requires skills that most basic science researchers are not taught.  Dr. Aldrich is formally and practically trained in translation requirements.  Understanding concepts such as validation of imaging devices and batch release of imaging agents enables researchers to discern which types of laboratory tests are necessary for moving a medical device or drug into the clinic.  Working with research groups from several other institutions, Dr. Aldrich served as the leader of the NCI validation core that authored a consensus paper describing some of the translation efforts needed for validation of optical imaging devices and molecular imaging agents.  This group was part of an effort by NCI to promote sharing and dissemination of translation practices amongst researchers.  In addition, she produced a “validation” paper that devised and described a process for assuring optical imaging agent purity, a parameter for which there was no FDA guidance available.

Besides the translational aspects, Dr. Aldrich is active in basic science investigations that employ the technologies she works to translate.  She has investigated the effects of inflammation on lymphatic function in mice, and found that cytokines act as systemic mediators of lymphatic pumping through iNOS-associated mechanisms.  Work by other groups has shown that inflammatory cytokines affect lymphatic function, but this study was the first to show that the effects are systemic, and defines a role for inflammation in some lymphatic diseases.

RESEARCH PROJECTS

  • Clinical studies of NIRF imaging of lymphatic architecture and function in health and disease
  • Validation in the context of translation
  • Inflammatory cytokine effects on systemic lymphatic function

SELECTED PUBLICATIONS

  • Aldrich MB, Sevick-Muraca EM.  Cytokines are systemic effectors of lymphatic function in inflammation. 2013. Cytokine 64:362-9.
  • Aldrich MB, Guilliod RG, Fife CE, Maus EA, Smith L, Rasmussen JC, Sevick-Muraca EM.  Lymphatic abnormalities in the normal contralateral arms of subjects with breast cancer-related lymphedema as assessed by near-infrared fluorescent imaging.  2012.  Biomedical Optics Express 3:1256-65.
  • Aldrich MB, Marshall MV, Sevick-Muraca EM, Lanza G, Kotyk J, Culver J, Wang LV, Uddin J, Crews BC, Marnett LJ, Liao JC, Contag C, Crawford JM, Wang K, Reisdorph B, Appelman H, Turgeon KD, Meyer C, Wang T.  Seeing it through:  translational validation of new medical imaging modalities.  2012.  Biomedical Optics Express 3(4):764-776.
  • Aldrich MB, Wang XJ, Hart A, Kwon SK, Sampath L, Marshall MV, and Sevick-Muraca, E.  Assessment of free dye in solutions of dual-labeled antibody conjugates for in vivo molecular imaging.  2010.  Molecular Imaging and Biology 13:32-42.
  • Aldrich MB, Davies-Venn C, Angermiller B, Robinson H, Chan W, Kwon K, Sevick-Muraca EM. Concentration of indocyanine green does not affect lymphatic function.  2012.  Lymphatic Research and Biology 10(1):1-5.

 Normal arm lymphatic vessel architecture