Histone 3 K27M mutated (H3K27M+) diffuse midline gliomas (DMGs) are a universally fatal pediatric brain cancer despite recently improved knowledge of the underlying biology. With relatively few advancements in treatment since targeted radiotherapy and a prognosis of generally less than one year to live, children diagnosed with DMGs are in great need of new therapeutic options. Chimeric antigen receptor (CAR) T cells have demonstrated remarkable clinical promise, particularly for blood cancers. To date, potency in solid tumors still remains limited.

Female cells undergo a naturally occurring mechanism to allow for dosage compensation, called X- chromosome Inactivation (XCI) so that X-linked genes are equally expressed in males. In this event, one of the two X chromosomes is randomly silenced due to XCI, which becomes transcriptionally inert. De novo variants in MECP2, a gene on the long arm of the X-chromosome, gives rise to Rett Syndrome (RTT) via a quasi-haploinsufficiency. RTT is a rare and progressive neurodevelopmental disorder that occurs predominantly in females.

The CRISPR-Cas9 system is a powerful tool that is revolutionizing how we understand and treat disease. Combining CRISPR-Cas9 genome editing with autologous stem cell transplantation has allowed the development of curative therapies for previously difficult-to-treat genetic diseases. In an effort to apply this technology to the treatment of an underrepresented disease, we set out to develop a novel CRISPR- Cas9-based therapy for the treatment of X-Linked Sideroblastic Anemia (XLSA). Patients with this disease develop red blood cells that fail to produce enough hemoglobin.

The heterozygous R132H mutation in the metabolic isocitrate dehydrogenase 1 (IDH1) gene is found in 1/3 of adult gliomas, the most common primary malignant brain tumor. Recent studies suggest that the R132H mutation converts to a passenger gene during tumor progression. Instead of targeting the IDH1 mutation itself, we performed a high-throughput screen to identify vulnerabilities in IDH1 mutant glioma cultures.

Mandibular fractures remain a challenging clinical entity and are commonly associated with injury of the inferior alveolar nerve (IAN). Previous research by our group has identified the mouse skeletal stem cell (mSSC) and demonstrated its role as enactors of bone generation during and during mandibular fracture repair and mandibular distraction osteogenesis, a postnatal regenerative paradigm. While it is known that denervation results in impaired tissue regeneration, the direct effect of denervation on stem cells that enact these processes is unknown.

Kristine focused on the isolation and functional characterization of fetal hematopoietic stem cells (HSCs) during her CIRM Bridges year in Dr. Irving Weissman’s laboratory at Stanford University. HSCs are responsible for the lifelong production of blood and immune cells. HSC transplant is clinically established as effective treatment in both malignant and non-malignant disease, but HSCs remain in short supply. Additionally, attempts to produce HSCs in vitro on a clinical scale have not be successful.

Stress Urinary incontinence (SUI) is a urological condition in which urine uncontrollably leaks out in response to daily physical activities. SUI negatively impacts an estimated 15 million and costs over 12 billion healthcare dollars annually. Both women and men are affected however, women have additional factors; childbirth, menopause, previous surgeries, and age-related muscular atrophy that contribute to developing SUI.

Ischemic injuries including coronary and peripheral arterial clots can lead to stroke or myocardial infarction and ultimately, death of the tissue. Attempts to re-vascularize these tissues has been an active area of study but thus far clinical trials using various cell types, or recombinant proteins have shown little efficacy. Previously in our lab, we identified two unique populations in mice which, when combined, gave rise to de novo vessels in vivo following ischemic injury.

Angelman syndrome (AS) is a rare neurological disorder caused by loss of Ube3a protein in neurons. In all individuals, this loss occurs from the paternal allele due to genomic imprinting; at around week 10 of neuronal development, a long noncoding RNA, Ube3a-ATS, is transcribed from the paternal allele. Ube3a-ATS physically overlaps paternal Ube3a, thereby blocking its transcription. Individuals with AS have a complete absence of Ube3a expression in the brain due to a maternal loss of function.

Osteoarthritis (OA) is a chronic disease characterized by a progressive loss of hyaline cartilage, leading to restricted movement and painful joints. Due to a lack of vasculature, low cellularity, and the low mitotic activity of chondrocytes, hyaline cartilage does not spontaneously regenerate. Microfracture (MF) surgery can be used to treat OA and works by stimulating production of de novo cartilage in the treated areas. However, fibrocartilage rather than hyaline cartilage forms in the area following surgery.