A5008012217- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Eosinophilic Disorders and Syndromes
- Hematopoietic Stem Cell Transplantation
- Epigenetics and DNA Methylation
- Retinoids in leukemia and cellular processes
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Histone Deacetylase Inhibitors Research
- Cytokine Signaling Pathways and Interactions
- Cell Image Analysis Techniques
- Multiple Myeloma Research and Treatments
- Viral-associated cancers and disorders
- Ubiquitin and proteasome pathways
Vanderbilt University Medical Center
2016-2025
Vanderbilt University
2016-2025
Vanderbilt-Ingram Cancer Center
2016-2022
Memorial Sloan Kettering Cancer Center
2022
UNC Lineberger Comprehensive Cancer Center
2008
University of Chicago
2006
George Washington University
1985
Washington University Medical Center
1985
University of Colorado Health
1981
Mayo Clinic
1981
Recently, the USA FDA has made a labeling change to drug information contained in carbamazepine. Owing recent data implicating HLA allele B*1502 as marker for carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis Han Chinese, recommends genotyping all Asians allele. This is seen high frequency many Asian populations other than but there are few on whether this severe outcome anyone Chinese. In fact, association not been found Caucasian patients. We review that...
Olutasidenib is a potent, selective, oral, small molecule inhibitor of mutant IDH1 (mIDH1) which induced durable remissions in high-risk, relapsed/refractory (R/R) mIDH1 AML patients phase 1/2 trial. We present pooled analysis from multiple cohorts the trial with R/R who received combination olutasidenib and azacitidine therapy. Adult mIDH1R132 150 mg twice daily plus standard-of-care (OLU + AZA) were evaluated for response safety. Sixty-seven OLU AZA. Median age was 66 years (range 28-82)...
Abstract Immune checkpoint inhibitors have improved outcomes for patients with numerous hematological and solid cancers. Hematologic toxicities been described, but the spectrum, timing, clinical presentation of these complications are not well understood. We used World Health Organization's pharmacovigilance database individual-case-safety-reports (ICSRs) adverse drug reactions, VigiBase, to identify cases hematologic complicating immune inhibitor therapy. identified 168 ICSRs...
Immunotherapies targeting the PD-1 pathway produce durable responses in many cancers, but tumor-intrinsic factors governing response and resistance are largely unknown. MHC-II expression on tumor cells can predict to anti-PD-1 therapy. We therefore sought determine how by promotes dependency. Using transcriptional profiling of anti-PD-1-treated patients, we identified unique patterns immune activation MHC-II+ tumors. In patients preclinical models, tumors recruited CD4+ T developed...
Clonal hematopoiesis (CH) is an age-associated phenomenon that increases the risk of hematologic malignancy and cardiovascular disease. CH thought to enhance disease through inflammation in peripheral blood.1 Here, we profile blood gene expression 66 968 single cells from a cohort 17 patients with 7 controls. Using novel mitochondrial DNA barcoding approach, were able identify separately compare mutant Tet methylcytosine dioxygenase 2 (TET2) methyltransferase 3A (DNMT3A) nonmutant...
To elucidate the relationship between Epstein-Barr virus (EBV) and rheumatoid arthritis (RA), we measured antibodies to RA-associated nuclear antigen (anti-RANA) three other EBV-related antigens in sera of RA patients controls. Our study groups consisted 89 with definite or classical RA, mean age 56, male/female ratio 47:42; 53 normal osteoarthritis controls, 51, 25:28. In addition anti-RANA, viral capsid (anti-VCA), early (anti-EA) EBV-associated (anti-EBNA). Anti-RANA was detected 71% but...
The monocyte phagocyte system (MPS) includes numerous monocyte, macrophage, and dendritic cell (DC) populations that are heterogeneous, both phenotypically functionally. In this study, we sought to characterize those diverse MPS phenotypes with mass cytometry (CyTOF). To identify a deep phenotype of monocytes, macrophages, DCs, panel was designed measure 38 identity, activation, polarization markers, including CD14, CD16, HLA-DR, CD163, CD206, CD33, CD36, CD32, CD64, CD13, CD11b, CD11c,...
For patients with high risk myeloid disease, allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy. Unfortunately, many of these relapse after HCT and have a limited survival. The recent approval venetoclax, an orally bioavailable BCL-2 inhibitor, resulted in significant responses treatment naïve acute leukemia (AML), off-label use relapsed/refractory setting increasing. We report outcomes 21 who underwent for relapsed AML, were treated venetoclax....
Abstract Clonal evolution in myelodysplastic syndrome (MDS) can result clinical progression and secondary acute myeloid leukemia (sAML). To dissect changes clonal architecture associated with this progression, we performed single-cell genotyping of paired MDS sAML samples from 18 patients. Analysis genotypes revealed patient-specific enabled the assessment mutational cooccurrence. We discovered that proceed via distinct patterns, classified as static or dynamic, dynamic architectures having...
Abstract Clonal hematopoiesis (CH) can be caused by either single gene mutations (eg point in JAK2 causing CHIP) or mosaic chromosomal alterations (e.g., loss of heterozygosity at chromosome 9p). CH is associated with a significantly increased risk hematologic malignancies. However, the absolute rate transformation on an annualized basis low. Improved prognostication urgently needed for routine clinical practice. We hypothesized that co-occurrence CHIP and mCAs same locus transforming...
Olutasidenib, a potent, selective, oral, mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor, is FDA-approved for relapsed/refractory (R/R) acute myeloid leukemia (AML). Here we report efficacy and safety of olutasidenib in 18 patients with m
Leukemic stem cells (LSCs) can acquire non-mutational resistance following drug treatment leading to therapeutic failure and relapse. However, oncogene-independent mechanisms of persistence in LSCs are incompletely understood, which is the primary focus this study. We integrated proteomics, transcriptomics, metabolomics determine contribution STAT3 promoting metabolic changes tyrosine kinase inhibitor (TKI) persistent chronic myeloid leukemia (CML) cells. Proteomic transcriptional...
Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While inclusions into prognostic models substantively advanced risk stratification, revelations emphasized the pivotal role immune dysregulation within bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for has not experienced breakthroughs seen other malignancies, partly...
The plasticity of AML drives poor clinical outcomes and confounds its longitudinal detection. However, the immediate impact treatment on leukemic non-leukemic cells bone marrow blood remains relatively understudied. Here, we conducted a pilot study high dimensional monitoring immunophenotype in AML. To characterize changes cell phenotype before, during, immediately after induction treatment, developed 27-antibody panel for mass cytometry focused surface diagnostic markers applied it to 46...
Discovering bioactive metabolites within a metabolome is challenging because there generally little foreknowledge of metabolite molecular and cell-targeting activities. Here, single-cell response profiles primary human tissue comprise platform used to discover novel microbial with cell-type-selective effector properties in untargeted metabolomic inventories. Metabolites display diverse mechanisms, including targeting protein synthesis, cell cycle status, DNA damage repair, necrosis,...
Clonal hematopoiesis (CH) is an age-associated phenomenon leading to increased risk of both hematologic malignancy and nonmalignant organ dysfunction. Increasingly available genetic testing has made the incidental discovery CH clinically common yet evidence-based guidelines effective management strategies prevent adverse health outcomes are lacking. To address this gap, prospective CHIVE (clonal inflammation in vasculature) registry biorepository was created identify monitor individuals at...
Advances in single-cell biology have enabled measurements of >40 protein features on millions immune cells within clinical samples. However, the data analysis steps following cell population identification are susceptible to bias, time-consuming, and challenging compare across studies. Here, an ensemble unsupervised tools was developed evaluate four essential types information, incorporate changes over time, address diverse monitoring challenges. The complementary properties characterized...
The nonimmune roles of Tregs have been described in various tissues, including the BM. In this study, we comprehensively phenotyped marrow Tregs, elucidating their key features and tissue-specific functions. We show that are migratory home back to marrow. For trafficking, use S1P gradients, disruption axis allows for specific targeting Treg pool. Following depletion, function phenotype both mesenchymal stromal cells (MSCs) hematopoietic stem (HSCs) was impaired. Transplantation also revealed...