Cell fate choices balancing proliferation and differentiation

All blood lineage cells are produced from a very small number of hematopoietic stem and progenitor cells in the bone marrow. The process of blood cell production (hematopoiesis) is powerful enough to produce billions of blood cells every second, and requires a tightly regulated program balancing cellular proliferation and differentiation. This complex process can wrong in several ways, leading to either leukemia or bone marrow failure. The production of red blood cells (erythropoiesis) is an ideal model for carefully choreographing the balance between proliferation and differentiation given that more erythrocytes are produced on a daily basis than any other cell type in the body and erythrocytes undergo one of the most complex differentiation processes in biology. We study how this process is regulated in normal hematopoiesis, how this process becomes dysregulated during disease, and how we can manipulate the balance of proliferation and differentiation to treat some of the most devastating disorders in medicine.

Stem cell transplantation

Swapping out a diseased hematopoietic system for a new healthy one through HSCT: hematopoietic stem cell transplantation (also known as BMT: blood and marrow transplantation) can cure most blood disorders. For other diseases that can affect various organs throughout the body, HSCT/BMT also has the potential to serve as a definitive cure by using engineered blood cells as a therapeutic delivery vehicle. However, HSCT/BMT comes with major risks that prevent widespread adoption for all the diseases it could potentially treat. We study the stem cell biology and immunology behind HSCT/BMT and seek to identify all-encompassing strategies to achieve zero-risk transplantation that could potentially cure 10% of all human diseases.

Evolution of blood cell biology with age

The hematopoietic system is responsible for delivering oxygen, stopping bleeding, healing wounds, establishing and sustaining immunity, and maintaining and repairing all tissues within the body. However, as human beings develop and age there are changing needs for the blood system based on the different challenges we face during different phases of life. We seek to understand how these changes to the hematopoietic system are intrinsically programmed and stimulated by extrinsic factors, as well as how the biology from one phase of life can be leveraged in a different phase of life for therapeutic purposes.

Point-of-care blood testing

The biotechnology and molecular medicine fields continue to create an ever expanding array of diagnostic tests to be deployed in advanced laboratory settings. Unfortunately, patients in low- and middle-income countries have had little access to these innovations. To contribute to global health equity efforts, we are undertaking efforts to adapt molecular testing to point-of-care blood tests that can be deployed in low-resource settings.

Recorded talks on our work

March 4, 2024: Hojun introducing the lab to UCSD at the Division of Regenerative Medicine seminar series. Many thanks to Rob Signer for the invitation.

https://www.youtube.com/watch?v=XXmglP_40nk

September 6, 2024: Hojun describing the therapeutic promise of blood and marrow transplantation at Rady Children’s Hospital Pediatrics Grand Rounds.

(skip to the 2:09 mark for the start of the talk)

September 9, 2024: Hojun talks with Izzy Ancharski from the Moores Cancer Center (MCC) Communications Department about the role that blood cell research and pediatrics plays in MCC’s mission.

Vimeo link