A5058778175- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Craniofacial Disorders and Treatments
- SARS-CoV-2 and COVID-19 Research
- RNA Research and Splicing
- Multiple Myeloma Research and Treatments
- Single-cell and spatial transcriptomics
- Cleft Lip and Palate Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- COVID-19 Clinical Research Studies
- Genomics and Chromatin Dynamics
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- dental development and anomalies
- Congenital heart defects research
- Cardiovascular Function and Risk Factors
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Histone Deacetylase Inhibitors Research
- SARS-CoV-2 detection and testing
- RNA modifications and cancer
Yale University
2022-2025
Yale Cancer Center
2022-2025
University of New Haven
2023-2024
University of Connecticut
2009-2023
Smilow Cancer Hospital
2022
UConn Health
2018-2021
Universidad Cristiana Autónoma de Nicaragua
2020
University of Vermont
2015-2016
University of Massachusetts Chan Medical School
2011-2016
Defects in patterning during human embryonic development frequently result craniofacial abnormalities. The gene regulatory programs that build the complex are likely controlled by information located between genes and within intronic sequences. However, systematic identification of sequences important for forming face has not been performed. Here, we describe comprehensive epigenomic annotations from tissues comparisons with multiple cell types. We identified thousands tissue-specific causal...
The Runx1 transcription factor, known for its essential role in normal hematopoiesis, was reported limited studies to be mutated or associated with human breast tumor tissues. increases concomitantly disease progression the MMTV-PyMT transgenic mouse model of cancer. Compelling questions relate mechanisms that regulate expression Here, we tested hypothesis dysregulation Runx1-targeting microRNAs (miRNAs) allows pathologic increase during cancer progression. Microarray profiling revealed...
Craniofacial disorders arise in early pregnancy and are one of the most common congenital defects. To fully understand how craniofacial arise, it is essential to characterize gene expression during patterning region. address this, we performed bulk single-cell RNA-seq on human tissue from 4-8 weeks post conception. Comparisons dozens other tissues revealed 239 genes strongly expressed development. Craniofacial-biased developmental enhancers were enriched +/- 400 kb surrounding these...
Stem cell phenotypes are reflected by posttranslational histone modifications, and this chromatin-related memory must be mitotically inherited to maintain identity through proliferative expansion. In human embryonic stem cells (hESCs), bivalent genes with both activating (H3K4me3) repressive (H3K27me3) modifications essential sustain pluripotency. Yet, the molecular mechanisms which epigenetic landscape is transferred progeny remain established. By mapping genomic enrichment of...
The COVID-19 pandemic created the urgent need to monitor risk of SARS-CoV-2 infection and mortality, evaluate immune responses novel vaccines. A foremost concern was unknown risks patients with cancer, considering their overall health, status interactions cancer therapies. U.S. National Cancer Institute, in partnership Institute Allergy Infectious Diseases, established Serological Sciences Network (SeroNet) as nation's largest coordinated effort identify establish standardized serology tests...
There is growing evidence that common variants and rare sequence alterations in regulatory sequences can result birth defects or predisposition to disease. Congenital heart are the most defect have a clear genetic component, yet only third of cases be attributed structural variation genome mutation gene. The remaining unknown could caused by sequences.
Abstract BACKGROUND Prostate‐specific antigen (PSA) is a pivotal downstream target gene of the androgen receptor (AR), and serum biomarker to monitor prostate cancer (PrCa) progression. It has been reported that PSA transactivates AR, but mechanistic requirements this response have not investigated. METHODS We studied localization PSA, Src in intracellular compartments synthetic (R1881)‐stimulated LNCaP C4‐2B PrCa cells, using immunofluorescence subcellular fractionation approaches. also...
The transition of human embryonic stem cells (hESCs) from pluripotency to lineage commitment is not fully understood, and a role for phenotypic transcription factors in the initial stages hESC differentiation remains be explored. From screen candidate factors, we found that RUNX1 selectively transiently upregulated early mesendodermal lineages. Transcriptome profiling functional analyses upon depletion established promoting cell motility. In parallel, discovered loss repression several...
Single-cell technologies offer a unique opportunity to explore cellular heterogeneity in hematopoiesis, reveal malignant hematopoietic cells with clinically significant features and measure gene signatures linked pathological pathways. However, reliable identification of cell types is crucial bottleneck single-cell analysis. Available databases contain dissimilar nomenclature non-concurrent marker sets, leading inconsistent annotations poor interpretability. Furthermore, current tools focus...
Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization unclear mechanisms. To study this process, we engineer a human model to track replication using fluorescently tagged cyclin B1 troponin T. Using time-lapse imaging, in vitro patterns recapitulate the mononuclear arrest observed vivo. Single-cell transcriptomics chromatin state analyses reveal that preceded sarcomere assembly, enhanced oxidative metabolism, DNA damage response, p53...
Abstract How to develop highly informative serology assays evaluate the quality of immune protection against coronavirus disease‐19 (COVID‐19) has been a global pursuit over past years. Here, microfluidic high‐plex immuno‐serolomic assay is developed simultaneously measure50 plasma or serum samples for50 soluble markers including 35proteins, 11 anti‐spike/receptor binding domian (RBD) IgG antibodies spanningmajor variants, and controls. This demonstrates quintuplicate test in single run with...
7559 Background: The B cell maturation antigen (BCMA)-targeted antibody drug conjugate belantamab mafodotin enhances cell-mediated antibody-dependent cellular cytotoxicity and phagocytosis. Elotuzumab, a signaling lymphocytic activation molecule family member 7 (SLAMF7) checkpoint inhibitor, activates NK cells induces cytotoxicity. Bela-Elo (NCT05002816) is an ongoing phase Ib/II trial evaluating the safety, tolerability preliminary efficacy of unique combination these two agents in patients...
We investigated immune cytopenia in multiple myeloma (MM) patients with concurrent acquired aplastic anemia (AA), focusing on three clinical cases treated plasma cell-directed therapy. All achieved partial response MM and one patient experienced complete resolution of AA. Two had improvement transfusion requirement but continued to suffer from severe AA, leading immunosuppressive therapy (IST) both patients.
Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to increase all-cause mortality and risk cardiomyopathy in patients with solid malignancies. CHIP also T cell activation heart failure patients. It is unclear whether can affect the immune checkpoint inhibitor (ICI) myocarditis cancer treated immunotherapy. Methods We enrolled tumors a prospective study, determined status at time enrollment through blood whole exome sequencing, assessed incidence ICI...
Abstract Background Global efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underlying cause disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well immune responses after vaccination across populations social dimensions prevention treatment strategies. Methods In United States, National Cancer Institute in partnership with Allergy Infectious Diseases, established SARS-CoV-2 Serological...
ABSTRACT The cellular and genetic mechanisms that coordinate formation of facial sensory structures with surrounding skeletal soft tissue elements remain poorly understood. Alx1, a homeobox transcription factor, is key regulator midfacial morphogenesis. ALX1 mutations in humans are linked to severe congenital anomalies the skeleton (frontonasal dysplasia, FND) malformation or absence eyes orbital contents (micro- anophthalmia). Zebrafish loss-of-function alx1 develop craniofacial ocular...
Summary Craniofacial disorders are among the most common of all congenital defects. A majority craniofacial development occurs early in pregnancy and to fully understand how defects arise, it is essential observe gene expression during this critical time period. To address we performed bulk single-cell RNA-seq on human tissue from embryonic 4 8 weeks post conception. This data comprises comprehensive profiling transcriptome developing face date. We identified 239 genes that were specifically...
Defects in patterning during human embryonic development frequently result craniofacial abnormalities. The gene regulatory programs that build the complex are likely controlled by information encoded genome between genes and within intronic sequences. However, early stages of have not been interrogated with functional genomics techniques, preventing identification sequences important for forming face. Here we describe comprehensive epigenomic annotations from tissues systematic comparisons...
Abstract During the COVID-19 pandemic, hematopoietic stem cell transplant (HSCT) recipients faced an elevated mortality rate from SARS-CoV-2 infection, ranging between 10-40%. The mRNA vaccines are important tools in preventing severe disease, yet their efficacy post-transplant setting remains unclear, especially patients subjected to myeloablative chemotherapy and immunosuppression. We evaluated humoral adaptive immune responses vaccination series 42 HSCT 5 healthy controls. Peripheral...