Abdul Karzai
A5073791049- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Acute Myeloid Leukemia Research
- Eosinophilic Disorders and Syndromes
- Chronic Myeloid Leukemia Treatments
- Sperm and Testicular Function
- Hormonal and reproductive studies
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Ovarian function and disorders
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Herpesvirus Infections and Treatments
- Cancer Genomics and Diagnostics
- Cytokine Signaling Pathways and Interactions
- Kruppel-like factors research
- Plant Reproductive Biology
- DNA Repair Mechanisms
Memorial Sloan Kettering Cancer Center
2019-2024
Johns Hopkins University
1989-1992
Abstract Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes MPNs, remissions rare, mutant allele burden does not substantively change chronic therapy. We hypothesized this is due to limitations current potently specifically abrogate JAK2 signaling. therefore developed a conditionally inducible mouse model...
We investigated the role of PRMT5 in myeloproliferative neoplasm (MPN) pathogenesis and aimed to elucidate key targets contributing MPN maintenance. is overexpressed primary cells, inhibition potently reduced cell proliferation ex vivo. was efficacious at reversing elevated hematocrit, leukocytosis, splenomegaly a model JAK2V617F+ polycythemia vera leukocyte platelet counts, hepatosplenomegaly, fibrosis MPLW515L myelofibrosis. Dual targeting JAK superior or inhibitor monotherapy, further...
While numerous studies have examined the response of immature rat Sertoli cells to specific hormones and growth factors, regulation mature in vitro has not been well because highly purified difficult isolate. We now describe a detailed method for isolating from (> 60 days age) rats generating primary cultures these greater than 90% purity. demonstrate that cell density, hormones, factors regulate synthesis or secretion two products, transferrin Cyclic Protein-2 (CP-2)/cathepsin L. Cell...
This review briefly describes the discovery and isolation of a novel Sertoli cell product, cyclic protein-2, (CP-2) generation an antiserum against this protein. Using antiserum, we demonstrated stage-specific change in synthesis CP-2 by cells within intact seminiferous tubules; is maximal at stages VI VIIa,b cycle minimal stage XII. That product was confirmed immunohistochemical analysis. Comparison transferrin immature (17-day) mature (75-day) tubules has documented significant increase...
Studies of the replication genome bacteriophage λ in vivo and vitro have provided us with a number fundamental insights about biological mechanisms used initiation regulation chromosomal DNA (for review, see Furth Wickner 1983; Echols 1990). Following its injection into sensitive Escherichia coli cell, linear, 48.5-kb chromosome is rapidly circularized converted by gyrase negatively supertwisted molecule. Initiation depends on two viral proteins, O P numerous proteins encoded host bacterium...
Cyclic Protein-2 (CP-2) is synthesized in a stage-specific manner by mature rat Sertoli cells within stage VI and VII seminiferous tubules. To determine how testicular maturation affects CP-2 synthesis, we cultured 20 cm of tubules encompassing all stages the cycle from rats 17, 35, 45, 75 days old. The greatest increase synthesis was found to occur between 35 45 exceeded that observed for transferrin sulfated glycoprotein (SGP)-2. Additionally, two-dimensional gel analysis indicated...
<p>Functional consequences of Jak2V617F reversion ex vivo</p>
<p>Functional characterization of Jak2RL knock-in/knock-out in vivo</p>
<p>Effects of Jak2V617F deletion on MPN stem cell fitness and disease transplantability</p>
<p>Differential gene expression responses of Jak2V617F deletion compared to JAK inhibitor therapy</p>
<p>Acute phenotypic and transcriptional changes following Jak2V617F reversion</p>
<p>Differential responses of Jak2V617F deletion compared to JAK inhibitor therapy in vivo</p>
<p>Assessment of tamoxifen toxicity on Jak2RL knock-in cells</p>
<p>Phenotypic characterization and validation of Jak2RL activation in vivo</p>
<p>Phenotypic characterization and Jak2V617F oncogenic dependency in the setting of concomitant Tet2 loss</p>
<p>Phenotypic characterization and Jak2V617F oncogenic dependency in the setting of concomitant Tet2 loss</p>