The new Hematologic Oncology Translational (HOT) laboratory, located on the second floor of the Cannon Research Building, is led by Belinda R. Avalos, MD, and Jonathan M. Gerber, MD. It is staffed by senior scientists Lawrence Druhan, PhD, and Sarah Baxter, PhD, along with two full-time technicians.
The major focus of the laboratory is to clarify basic mechanisms regulating normal and cancerous blood cell production, and use this information to develop novel methods for predicting cancer relapse and treatment strategies that improve survival for patients with hematologic malignancies.
Our research focuses on the following disorders:
The laboratory is one of only a few in the world with expertise in isolating leukemia stem cells, the cells responsible for initiation and relapse of leukemia. The lab is leveraging this expertise – as well as our strengths in molecular biology, growth factor receptors and cell signaling – to identify unique properties of cancer stem cells that distinguish them from normal stem cells so we can target malignant - but not normal - stem cells.
We are also investigating the molecular mechanisms in the incidence and aggressiveness of blood cancers as they relate to age, race and ethnicity. These studies are incorrelation new clinical trials available to patients at Levine Cancer Institute. In addition, we are conducting studies with physicians at Levine Children's Hospital on pediatric leukemias and hematopoietic cell transplantation.
Hunter M and Avalos BR. Granulocyte colony-stimulating factors mutations in severe congenial neutropenia transforming to acute myelogenous leukemia confer resistance to apoptosis and enhance cell survival. Blood 95(6): 2132-2137, 2000. PMID:10706885
Druhan LJ, Ai J, Massullo P, Kindwall-Keller T, Ranalli MA, and Avalos BR. Novel mechanism of G-CSF refractoriness in patients with severe congenital neutropenia. Blood 2005, Jan. 15;105(2): 584-591. PMID:15353486
Massullo P, Druhan LJ, Bunnell BA, Hunter MG, Robinson J, and Avalos BR. Aberrant Subcellular Targeting of the G185R Neutrophil Elastase Mutant Associated with Severe Congenital Neutropenia Induces Premature Apoptosis of Differentiating Promyelocytes. Plenary Paper, Blood. 2005 May 1;105(9):3397-404. PMID:15657182
Ai J, Druhan LJ, Hunter MG, Loveland MJ, Avalos BR. LRG-Accelerated differentiation defines unique G-CSFR signaling pathways downstream of PU.1 and C/EBPε that modulate neutrophil activation. J Leuk Biol, 2008 May; 83(5); 1277-85. PMID:18272588.
Ai, J, Druhan LJ, Loveland M, Avalos BR. G-CSFR ubiquitination critically regulates myeloid cell survival and proliferation. PLoS ONE, 3(10): e3422. doi:10.1371/journal.pone.0003422, 2009. PMID:18923646.
Gerber JM, Qin L, Kowalski J, Smith BD, Griffin CA, Vala MS, Collector MI, Perkins B, Zahurak M, Matsui W, Gocke CD, Sharkis SJ, Levitsky HI, Jones RJ. Characterization of chronic myeloid leukemia stem cells. Am J Hematol. 2011 Jan;86(1):31-7. PMID: 21132730.
Gerber JM, Smith BD, Ngwang B, Zhang H, Vala MS, Morsberger L, Galkin S, Collector M, Perkins B, Levis MJ, Griffin CA, Sharkis SJ, Borowitz MJ, Karp JE, Jones RJ. A clinically relevant population of leukemic CD34+CD38- cells in acute myeloid leukemia. Blood 2012 Apr; 119(15):3571-7. PMID: 22262762
Gerber JM, Gucwa JL, Esopi D, Gurel M, Haffner MC, Vala M, Nelson WG, Jones RJ, Yegnasubramanian S. Genome-wide comparison of the transcriptomes of highly enriched normal and chronic myeloid leukemia stem and progenitor cell populations. Oncotarget. 2013 May;4(5):715-28. PMID:23651669
Ghiaur G, Yegnasubramanian S, Perkins B, Gucwa JL, Gerber JM, Jones RJ. Regulation of human hematopoietic stem cell self-renewal by the microenvironment's control of retinoic acid signaling. Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16121-6. PMID:24043786