Monica L Guzman

Leukemia can initiate from early oncogenic events in hematopoietic stem/progenitor cells, such events lead to the accumulation of pre-leukemia hematopoietic stem/progenitor cells that eventually can acquire subsequent mutations resulting in transformed malignant stem/progenitor cells that can give rise to leukemia.  Acute myeloid leukemia is a disease with still very poor outcomes, despite that most patients can achieve complete remission, the majority will relapse and eventually die of disease.  

Figure 1

Such poor outcomes are attributed to the inability to eliminate malignant stem/progenitor cells.  Thus, the laboratory focuses on (1) implementing methodologies that allow for the detection of residual disease using flow cytometry or next generation sequencing.   (2) implementing methodologies that mimic the microenvironment of malignant hematopoietic cells to assess stem/progenitor biological features or sensitivity to drug treatment ex vivo. (3) Testing novel therapeutic approaches to target such malignant population of cells; such approaches include chimeric antigen receptor T cells, epichaperome inhibitors and other targeted therapies using in vitro and in vivo models (4) Implementing microfluidic devices to understand the impact of early oncogenic events in hematopoietic cells. 

Figure 2

Current Projects:

• 3D systems to mimic the tumor microenvironment
• Improving CAR T cells responses using combinatorial approaches
• Epichaperome inhibitors as a therapeutic approach for leukemia and myeloma
• Clonal hematopoiesis
• Measurable residual disease