Shilpa Hattangadi, MD

Assistant Professor of Pediatrics (Hematology / Oncology) and of Pathology; Assistant Professor, Pathology

Research Departments & Organizations

Pediatrics: Pediatric Hematology & Oncology

Pathology

Yale Cancer Center: Genomics, Genetics, and Epigenetics

Yale Stem Cell Center

Office of Cooperative Research

Research Interests

Chromatin Immunoprecipitation; Disease Models, Animal; Erythroid-Specific DNA-Binding Factors; Erythropoiesis; Hematologic Diseases; Hematopoiesis; Heterochromatin; Histone Deacetylases; Histones; Microscopy, Confocal; Nucleocytoplasmic Transport Proteins

Research Summary

We are focused on understanding the terminal stages of normal red blood cell development, from terminally committed progenitors to circulating red blood cells (RBCs). This is important (1) to learn why certain RBC disorders develop in the first place, but also (2) to help overcome challenges in treatment of these disorders as well as develop new ones. Our most recent focus on red blood cell development has been on how enucleation is dependent on nuclear protein export, how the nucleus condenses, and how histones are replaced in the condensing red cell nucleus before it is extruded.

We are also interested in identifying new genetic causes and/or modifiers of bone marrow failure syndromes and are interested in creating new mouse models of cytopenias found in children using the humanized mouse system here at Yale. We are currently pursuing one such regulator which is a post-translational modifier of hematopoietic regulators and has been found to be mutated in MDS and AML.

Clinical Trials

Conditions Study Title
Brain and Nervous System A Phase 2 Study of Veliparib (ABT-888) and Local Irradiation, Followed by Maintenance Veliparib and Temozolomide, in Patients With Newly Diagnosed High-Grade Glioma (HGG) Without H3 K27M or BRAFV600E Mutations
Brain and Nervous System A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or Crizotinib Added to Intensive Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma (NBL)
Bones and Joints, Kidney, Soft Tissue, Pediatrics Phase 3 Accelerated BEP: A Randomised Phase 3 Trial of Accelerated Versus Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumors
Other Hematopoietic, Pediatrics A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Non-Malignant Disease Using a Reduced-Intensity Preparatory Regime
Pediatrics A Phase 1/2 Study of VX15/2503 in Children, Adolescents, or Young Adults With Recurrent or Relapsed Solid Tumors
Bones and Joints, Brain and Nervous System, Leukemia, not otherwise specified, Leukemia, other, Lymphoid Leukemia NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) Screening Protocol
Lymphoid Leukemia A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia
Hodgkin's Lymphoma, Pediatrics Risk-based, Response-adapted, Phase II Open-label Trial of Nivolumab + Brentuximab Vedotin (N + Bv) for Children, Adolescents, and Young Adults With Relapsed/Refractory (R/R) CD30 + Classic Hodgkin Lymphoma (cHL) After Failure of First-line Therapy, Followed by Brentuximab + Bendamustine (Bv + B) for Participants With a Suboptimal Response (CheckMate 744: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation)
Anus, Breast - Female, Breast - Male, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Pediatrics, Cervix, Urinary Bladder A Randomized Phase 3 Study of Vincristine, Dactinomycin, Cyclophosphamide (VAC) Alternating With Vincristine and Irinotecan (VI) Versus VAC/VI Plus Temsirolimus (TORI, Torisel, NSC# 683864) in Patients With Intermediate Risk (IR) Rhabdomyosarcoma (RMS)
Other Male Genital, Ovary Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Kaposi's sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Melanoma, skin, Mycosis Fungoides, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Pediatrics, Cervix, Urinary Bladder A Phase I/II Study of Pembrolizumab (MK-3475) in Children With Advanced Melanoma or a PD-L1 Positive Advanced, Relapsed or Refractory Solid Tumor or Lymphoma (KEYNOTE-051)
Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Kaposi's sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Lymphoid Leukemia, Melanoma, skin, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Cervix, Urinary Bladder NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors or Lymphomas
Brain and Nervous System, Pediatrics A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma
Bones and Joints, Brain and Nervous System, Eye and Orbit, Hodgkin's Lymphoma, Kidney, Leukemia, other, Liver, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkin's Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Small Intestine, Soft Tissue, Pediatrics The Project: Every Child Protocol: A Registry, Eligibility Screening, Biology and Outcome Study
Other Respiratory and Intrathoracic Organs, Pediatrics Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment (HEART)
Brain and Nervous System, Pediatrics Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma
Brain and Nervous System, Pediatrics Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Younger Patients With Newly Diagnosed Ependymoma
Leukemia, not otherwise specified, Pediatrics Risk-Stratified Randomized Phase III Testing of Blinatumomab in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)
Brain and Nervous System, Phase I, Pediatrics A Study Comparing Two Carboplatin Containing Regimens for Children and Young Adults With Previously Untreated Low Grade Glioma

Selected Publications

See list of PubMed publications

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Contact Info

Shilpa Hattangadi, MD
Mailing Address
Pediatric Hematology & OncologyPediatric Hematology-Oncology
333 Cedar Street

New Haven, CT 06520
Erythroid Terminal Differentiation

A set number of characteristic cell divisions (3 in mouse, 4 in humans) from the progenitor to the final erythroblast result in decreased cell size. A distinct expression program results in hemoglobin production, making the cytoplasm more eosinophilic. Nuclear condensation ensues and culminates in enucleation only in mammals. We study this last step of terminal erythropoiesis.