Marius Wernig, MD, PhD

May 4, 2022

By Christopher Vaughan

A record 17 institute researchers submitted proposals this year for in search of funding via Stinehart Reed awards. After thorough review by a panel of outside experts, five of those proposals garnered the prestigious awards, which are only available to institute members. 

For ten years, institute researchers have found support from the Stinehart Reed foundation for projects that show great promise of producing high-impact discoveries. These research projects are often too speculative or new to have accumulated supporting data that could lead to larger grants from established funding sources like the NIH. The only restrictions on the research, besides needing to be proposed by an institute member, is that the work be generally in the fields of stem cell science or regenerative medicine. Most years, Stinehart Reed grantees receive $200,000, paid at the rate of $100,000 a year over two years. 

This year, the Stinehart Reed winners proposed projects over a broad range of scientific projects, addressing problems afflicting all ages, from newborns to seniors. 

Perhaps no other subject inspires the public interest as much as the idea of regenerative therapy for aching joints. But so far, what passes for “stem cell therapy” for worn knees and hips have only been unproven, unpromising treatments using blood cells or mesenchymal cells. A few years ago, institute researchers Charles Chan, PhD, Michael Longaker, MD and colleagues discovered the human skeletal stem cell, from which all bone, cartilage and stromal cells come. Now, Chan has won a Stinehart Reed grant to build on this discovery by activating existing but inactive skeletal stem cells in the joint and guiding their growth so that they create regenerate cartilage. Current treatments can only generate a scar-like material called fibrocartilage,” Chan said. “What we’ve shown in mice is that we can generate true cartilage in the joints.” The Stinehart Reed award will help Chan and his colleagues do the some of the work necessary to bring this potential treatment to human clinical trials.

Irv Weissman, MD was awarded a grant to study clonal competition among brain stem cells. It turns out that not all stem cells are equal. Some stem cells acquire mutations that allow them to multiply more and survive better than other stem cells of the same type. For instance, supercompetitive mutant blood stem cells can push out other blood stem cells until, in some case, a person’s whole blood and immune system arises from just one clone. It is thought that such clonal competition in blood stem cells help lead to leukemias and diseases like atherosclerosis. Weissman and his colleagues hypothesize that a similar competition is taking place among neural stem cells, and that supercompetitive neural stem cells are helping give rise to brain cancer as well as neuropsychiatric and neurodegenerative disorders. 

Marius Wernig, MD, PhD, proposed investigating the activity of a brain cell receptor called TREM2, which has been tied to neurodegenerative diseases. In the central nervous system TREM2 (which stands for Triggering Receptor Expressed in Myeloid Cells 2) is exclusively found on microglial cells, which act as immune and housekeeping cells in the brain. Despite the seeming importance of TREM2, what we know about the receptor comes from studying a very different mouse molecule. Wernig proposes to study human microglial cells and their interaction with human neural tissue inside a mouse model. He want’s to understand why human TREM2 is so important is stopping neurodegeneration, and to find it’s role in the communication that happens between different cell types in the brain. 

Roel Nusse, PhD, wants to understand what controls the growth of the liver in early postnatal life. The liver is a unique organ in that it not only grows to a certain size and then stops, but if a portion is cut away, the liver will regenerate itself until it reaches that size again. Nusse has postulated that liver size is governed by the number of functional units call lobules. But what controls the number of lobules that develop? Nusse and his colleagues, which include institute member Kristy Red-Horse, PhD, Nusse lab member Dicle Azzizoglu, PhD, and UC Santa Cruz researcher (and former institute trainee) Camilla Forsberg, PhD, want to study the molecular mechanisms that govern lobule growth. “The understanding we gain from this work will directly inform the ongoing organ repair and vascularization efforts in regenerative medicine,” Nusse said.

Krabbe disease is a rare and often fatal neurodegenerative disorder in children, caused by a genetic defect in an enzyme that the body uses to break down fatty molecules called lipids. Shortly after birth, old lipids start building in the brain, killing nerve cells. Institute researcher Natalia Gomez-Ospina, PhD has won a Stinehart Reed award to help create blood stem cells and progenitor cells that are engineered to produce the enzyme missing in Krabbe disease. Eventually, clinicians may be able to take cells from these kids, engineer the cells to make the missing enzyme, and give them back to the patients to treat the disorder. 

Institute director Irv Weissman notes that over ten years, Stinehart Reed awards have advanced stem cell research along a number of fronts, and the most recent awards are likely to be equally successful. “Stinehart Reed awards have been a huge boon for our institute members, and for stem cell science,” Weissman said.