2012 Outstanding Leadership Award: Dr. Lynn Hlatky

Dr. Lynn Hlatky is an internationally known radiobiologist and cancer biologist. She received her PhD from the University of CA, Berkeley and trained in heavy ion radiobiology at Lawrence Berkeley Laboratory. She then was recruited to Harvard Medical School where she was faculty in Dept. of Radiation Oncology for a decade and half, before founding a Center of Cancer Systems Biology at Tufts Univ. School of Medicine.

Dr. Hlatky has long been involved in the quantitative and empirical study of radiation damage effects at the cellular and chromosomal levels, as well as the dynamical aspects of tumor development. For radiations demonstrating linear kill kinetics, she was the first to establish that any form of protracted dosing to an asynchronous cell population would be asymptotically more suppressive than an acute dose of the same magnitude [Hahnfeldt P and Hlatky L. Cell resensitization during protracted dosing of heterogeneous cell populations. Radiat Res 150:681-687, 1998]. She followed this up by showing that uniform dosing was optimal in this regard [Hahnfeldt P, Folkman J and Hlatky L. Minimizing long-term tumor burden: the logic for metronomic chemotherapeutic dosing and its antiangiogenic basis. J Theor Biol 220: 545-554, 2003].

Her lab has considerable expertise in angiogenesis and was also the first to show the expression of the major angiogenic factor, vascular endothelial growth factor (VEGF) in cells following irradiation [Hlatky L, Hahnfeldt P, Tsionou C, Coleman CN. Vascular endothelial growth factor: environmental controls and effects in angiogenesis. Br J Cancer 74(Suppl. XXVII):S151-6, 1996]. These earlier works highlighted the role of both endothelial and stromal cells in the radiation response of tumors. In the decade that followed, Dr. Hlatky’s lab uncovered many novel corollaries in both the angiogenic and radioresponse of tumor populations. Demonstrating a novel relationship between diversity in radioresponse over tumor populations under cell stress, her lab demonstrated the diversity in cellular radioresponse under conditions of environmental stress (using “sandwich cultures” designed to develop a self-imposed, gradated ischemia across the cell population) was reduced, then sharply increased, after mimicking reperfusion through introduction of oxygen/nutrients to the cultures [Hlatky L, Van Buren T, Hahnfeldt P. Quantifying intercellular radioresponse diversity in irradiated sandwich cultures via micronucleus expression. Int J Radiat Biol 1995;67:541-8].

Her latest work, in collaboration with Professor Rainer K. Sachs, refutes the long-held paradigm of a single-cell origin for chronic myelogenous leukemia, a notable radiation-inducible cancer. They demonstrated a statistically better fit to CML incidence when CML is considered to have a two-cell origin [Sachs RK, Johnsson K, Hahnfeldt P, Luo J, Chen A, Hlatky L. A multicellular basis for the origination of blast crisis in chronic myeloid leukemia. Cancer Res 71(8):2838-47, 2011]. The study has far-reaching implications on the role of cell-cell interactions in carcinogenesis.

Dr. Hlatky’s lab currently focuses on the study of cancer systems biology, with focus on investigations integrating carcinogenesis with radiobiology.