Six institute researchers win grants totaling $1 million from the Stinehart Reed Foundation

Christopher Vaughan

October 20, 2020    

Fourteen principal investigators at the Institute for Stem Cell Biology and Regenerative Medicine recently competed for $1 million in funding to support their research. The research grants were donated by the Stinehart Reed Foundation exclusively for the use by members of the institute. 

 “For many years, this funding from the Stinehart Reed Foundation has provided essential support for some of the most innovation research projects at the institute,” said institute director Irv Weissman, MD. “These projects are extremely promising, but due to a very competitive funding environment they may not otherwise get the funding they deserve.”

The Stinehart Reed funding was divided into five grants of $200,000 each, paid out over two years. The fourteen proposals were evaluated and scored by a group of outside experts. This year, there was an unusual tie for the 5th place grant. The researchers who were tied for fifth place agreed to split the award, with the result that six grants instead of five were awarded this year. 

The winning grants and investigators were as follows:

Kyle Loh, PhD

Two distinct developmental origins for the mammalian brain, with implications for development, cancer and evolution

It is a profound biological mystery how all the vast complexity of the adult brain emerges from a tiny pool of progenitors during embryonic development. Loh and his colleagues propose that the adult brain is a composite organ arising from two different streams of developmental progenitors, in contrast to the prevailing model of brain development. The Loh lab will use genetic lineage tracing to study whether there are two distinct developmental progenitors that give rise to the adult mouse brain. If so, they ask, is the existence of two brain progenitors conserved in humans? Loh is also interested in generating hindbrain neurons in vitro for further study.

Joanna Wysocka, PhD

Uphill on Waddington’s epigenetic landscape: Expansion of cellular potency during cranial neural crest development

Cell differentiation proceeds via a continuous lineage restriction process where cell potential is progressively reduced as the embryo develops, a concept visualized by Conrad Waddington as a marble rolling down the hill in his famed epigenetic landscape. In early development, pluripotent cells can become all sort of different kinds of cells, but as they develop, in effect picking a distinct pathway down the developmental landscape, they narrow their options for future development. Cranial neural crest cells have a remarkable ability to expand their potential developmental options, unlike most other kinds of cells. Dr. Wysocka’s research aims to use cranial neural crest development to understand how cellular potency expands during development.

Hiro Nakauchi, MD, PhD

Using non-conditioned HSC transplantation to generate novel immunocompetent xenograft models

A major goal of Dr. Nakauchi’s research is to apply stem cell-based technologies to overcome barriers in biomedicine and develop new therapies for human disease. With this grant, Dr. Nakauchi and his colleagues propose applying their recently developed ability to expand hematopoietic stem cell populations outside the body, their non-conditioned transplantation methods, to generate immunocompetent mice for modeling human cancers.

Philip Beachy, PhD

Death by mesenchyme: decoding cellular diversity to discover precise interventions in fibrosis

Fibrosis-induced organ failure is the ultimate cause of up to 45% of adult deaths, and is the end-stage of many fatal diseases including cardiovascular, lung, kidney and cirrhotic liver disease. Our inability to intervene in fibrotic disease is caused by an insufficient understanding of the underlying molecular and cellular bases of fibrosis. Dr. Beachy’s project will involve understanding the cells that make up normal and fibrotic tissue, and then studying ways to manipulate the development of specific cellular subtypes.

Gerlinde Wernig, MD

Preclinical evaluation of immune strategies for COVID19 to interject inflammatory processes contributing not only to acute morbidities and mortalities but also lung fibrosis in a humanized mouse model grafted with fetal lung, bone marrow, liver, and thymus

Much of the pathogenesis of COVID19 is attributed to excessive inflammatory response. One of the interleukins (IL-6) has been emerging as one of the key mediators of severe COVID19 in patients, and antibodies blocking IL-6 have shown therapeutic benefits. The cytokine, chemokine and transcriptional responses elicited in response to Sars-CoV-2 activate the inflammatory process in the lungs and cause pulmonary fibrosis in people who recover, as we know from prior Sars-CoV infections. Gerlinde Wernig’s lab has already been studying inflammatory processes in the lungs in the context of aging and lung fibrosis, and now they propose conducting an investigation of such mechanisms in COVID19 illness. Her goal is to identify disease mediators and develop therapeutic strategies to minimize the lung damage caused in response to SARS-CoV-2.

Marius Wernig, MD, PhD

A cell therapy for frontotemporal dementia

Frontotemporal dementia is an inherited disease that is pathologically characterized by the degeneration of the frontal and temporal lobes of the cortex, leading to social, behavioral, and language deterioration such as loss of empathy, disinhibition, repetitive compulsive behavior, frequent, abrupt mood changes and speech difficulties. It is now known that some of the most common causes for FTD are heterozygous loss-of-function mutations in the human GRANULIN (GRN) gene and other genes. Marius Wernig and his colleagues are trying to see if they can rescue mice undergoing brain deterioration by replacing microglia that have mutant GRN genes. They also hope to develop a microglia replacement strategy devoid of the toxicity associated with standard bone marrow replacement protocols.