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Karen-Sue Carlson Laboratory

Assistant Investigator Karen-Sue Carlson, MD, PhD, studies the mechanisms that direct cell development in the bone marrow.

Research Overview

 

Stem Cell Biology & Hematopoiesis Research at Versiti Blood Research Institute

Blood cell production begins in the bone marrow and is supported by a wealth of factors, otherwise referred to as the “hematopoietic niche.” The peripheral nervous system (PNS) is an important component of this niche. Sensory, sympathetic and parasympathetic branches of the PNS all innervate the bone marrow and transmit signals between the central nervous system and marrow to coordinate blood cell production and release into the peripheral circulation.

                       

We actively collaborate with other laboratories at Versiti Blood Research Institute to study hematopoietic development and malignancy, including those of: Sid Rao, MD, PhD; Hartmut Weiler, PhD; Nan Zhu, PhD; and John Pulikkan, PhD.

The central focus of my laboratory is to understand (1) the developmental cues that direct PNS fibers to engage with the bone marrow; (2) the mechanisms by which PNS-glial cells, i.e. Schwann cells, contribute to hematopoietic regulation; and (3) biological factors critical to maintaining these nerve fibers around and within the bone marrow.

 
Illustration of bone marrow blood vessel.A picture of a bone marrow blood vessel (pink and red) with adjacent GFP-positive Schwann cells. Cell nuclei are in blue.

By learning how “healthy” bone marrow develops, we will be able to apply this knowledge to blood cell malignancies, such as acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), in which bone marrow innervation is disordered by pre-existing conditions, medications and by the cancers themselves. Our long-term goal is to use this new knowledge to help treat and perhaps even prevent bone marrow cancers like AML and ALL.

Our laboratory has two primary projects:

  1. Schwann cell-dependent regulation of hematopoiesis: Schwann cells are the primary glial support cells for the PNS. Their development from Schwann cell precursors is tightly regulated by autocrine extracellular matrix production. Using a genetic model of Schwann cell developmental arrest, we have identified specific blood cells and other components of the bone marrow niche that require physiologic Schwann cell development.
  2. Mechanisms of neuropathy in AML: We are using murine models of AML to help define the mechanism(s) by which this type of acute leukemia causes peripheral neuropathy in and around the bone marrow. We are specifically interested in the impact of AML on Schwann cell function and survival.
Micrograph showing bone marrow innervation.

Green = Schwann Cell (GFP); Magenta = Axon (Neurofilament); Blue = Nuclei (DAPI)

Micrograph showing bone marrow innervation by peripheral nerve fibers.

Principal Investigator

Funding

1R03HL155174-01 Carlson (PI); 12/1/2020--11/30/2022 NIH/NHLBI Schwann Cell Regulation of Hematopoiesis This project will examine the role of peripheral nerve support-cells, i.e. Schwann Cells (SCs), in bone marrow innervation and regulation of blood cell production. Role: Principal Investigator

MCW Cancer Center Team Science Award Hari (PI); 3/1/2021—2/28/2023 Leveraging the biology of cancer health disparities to improve outcomes in multiple myeloma Role: Co-Investigator with Dr. Sridhar Rao (Project IV)—MDS/AML in Multiple Myeloma This project will identify the mechanism(s) by which Multiple Myeloma and related plasma cell disorders induce myeloid malignancies and the impact that stress has upon the evolution of the myeloid disorder.

Philanthropic Funding

Carlson (PI); 04/01/2020 –12/31/2021 Froedtert Hospital and the Scott Garrett Leukemia Research Foundation Neural Regulation of AML This project will determine whether Schwann cells isolated from patients and mice are differentially regulated by leukemic versus steady-state hematopoiesis. Role: Principal Investigator

Carlson (PI); 04/01/2020 –ongoing MCW Paulette Kroll Leukemia Research Fund Role: Principal Investigator

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