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James A. Hoxie, MD

James A. Hoxie, MD Physician

Professor of Microbiology Professor of Medicine

Dr. Hoxie is employed by Penn Medicine.

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Clinical Specialties

Specialty:

  • Hematology
  • Medical Oncology

Programs & Centers:

Board Certification:

  • Internal Medicine, 1979
  • Medical Oncology, 1981

Clinical Expertise:

  • Acute Lymphocytic Leukemia
  • Acute Myelogenous Leukemia
  • Acute Promyelocytic Leukemia
  • Adenocarcinoma of the Head and Neck
  • Adjuvant Chemotherapy
  • Adrenal Neoplasm
  • Adult T-Cell Leukemia
  • Adult T-Cell Lymphoma
  • AIDS Related Malignancies
  • All Cancer Types
  • Amyloidosis
  • Anal Cancer
  • Anaplastic Cancer of Thyroid
  • Anaplastic Large Cell Lymphoma
  • Anemia
  • Anemia and Bone Marrow Disorders
  • Anemia of Chronic Disease
  • Anemia of Pregnancy
  • Anticoagulation
  • Antiphospholipid Syndrome
  • Antithrombin Deficiency
  • Aplastic Anemia
  • Autoimmune Hemolytic Anemia
  • B12 Deficiency Anemia
  • Bile Duct Cancer (Cholangiocarcinoma)
  • Biological Targeted Therapy
  • Bladder Cancer
  • Bleeding Disorders
  • Blood Cancer
  • Blood Clot
  • Blood Clotting Disorders (Blood Coagulation)
  • Blood Disorders
  • Blood Platelet Disorders
  • Bone Marrow Biopsy
  • Bone Marrow Failure Syndromes
  • Bone Sarcoma
  • Bone Tumors
  • Brain Tumors
  • Breast Cancer
  • Burkitt Lymphoma
  • Cancer Chemotherapy
  • Cancer During Pregnancy
  • Cancer Pain
  • Cancer Survivor
  • Carcinoid Tumors
  • Carcinoma In Situ of Breast
  • Carcinoma of Unknown Primary
  • Castleman Disease
  • Catastrophic Antiphospholipid Syndrome
  • Cervical Cancer
  • Chronic Lymphocytic Leukemia
  • Chronic Myelocytic Leukemia
  • Chronic Myelomonocytic Leukemia
  • Clinical Trials
  • CNS Lymphoma
  • Coagulation Disorders
  • Cold Agglutinin Disease
  • Colon Tumors
  • Colorectal Cancer
  • Cooley's Anemia
  • Cryoglobulinemia
  • Cutaneous Lymphoma
  • Deep Thrombophlebitis
  • Deep Vein Thrombosis
  • Diamond Blackfan Anemia
  • Dyskeratosis Congenita
  • Endocrine Complications of Cancer Therapy
  • Endometrial Cancer
  • Eosinophilic Granuloma
  • Erdheim-Chester Disease
  • Esophageal Cancer
  • Essential Thrombocytosis
  • Ewings Sarcoma
  • Factor Eight Disorder
  • Factor Nine Deficiency
  • Factor V Leiden
  • Fallopian Tube Cancer
  • Familial Aplastic Anemia
  • Fanconi Anemia
  • Folic Acid Deficiency
  • Follicular Cancer of Thyroid
  • Gallbladder Cancer
  • Gastrointestinal Cancer
  • Gastrointestinal Stromal Tumors (GIST)
  • Gestational Trophoblastic Disease
  • Giant Cell Tumor of the Bone
  • Glioblastoma
  • Glioma
  • Glucose-6-Phosphate Dehydrogenase Deficiency
  • Graft Versus Host Disease
  • Hairy Cell Leukemia
  • Hand-Foot Syndrome
  • HELLP Syndrome
  • Hematologic Malignancies
  • Hemochromatosis
  • Hemoglobinopathies
  • Hemolytic Anemia
  • Hemolytic Uremic Syndrome
  • Hemophilia
  • Heparin-Induced Thrombocytopenia
  • Hereditary Cancer Risk
  • Hereditary Spherocytosis
  • Histiocytosis
  • Hodgkin Lymphoma
  • Hypercoagulable State
  • Hypogammaglobulinemia
  • Idiopathic Thrombocytopenic Purpura
  • Immunotherapy
  • Inflammatory Breast Cancer (IBC)
  • Intraocular Lymphoma
  • Iron Deficiency Anemia
  • Iron Metabolism Disorders
  • Kaposi Sarcoma
  • Kidney Cancer
  • Large Granular Lymphocytic Leukemia
  • Laryngeal Cancer
  • Leiomyosarcoma
  • Leukemia
  • Leukocytosis
  • Leukopenia
  • Light Chain Disorders
  • Liver Cancer
  • Lung Cancer
  • Lupus Anticoagulant
  • Lymphoma
  • Lymphopenia
  • Male Breast Cancer
  • Malignant Neoplasm of the Ureter
  • Marginal Zone Lymphoma
  • Maternal Anticoagulation
  • Maternal Hematologic Disorders
  • Maternal Thrombophilia
  • Mediastinal Lymphoma
  • Medullary Cancer of Thyroid
  • Melanoma
  • Merkel Cell Carcinoma
  • Mesothelioma
  • Monoclonal Gammopathy of Undetermined Significance
  • Mouth Cancer (Oral Cancer)
  • Mucosa-Associated Lymphoid Tissue Lymphoma
  • Mucosal Melanoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes (MDS)
  • Myeloproliferative Neoplasms (MPN)
  • Neoadjuvant Chemotherapy
  • Neuroendocrine Tumors
  • Neutropenia
  • Non-Hodgkin Lymphoma
  • Non-Small Cell Lung Cancer
  • Oropharyngeal Cancer
  • Osteosarcoma
  • Ovarian Cancer
  • Pancreatic Cancer
  • Pancytopenia
  • Papillary Cancer of Thyroid
  • Paroxysmal Nocturnal Hemoglobinuria
  • Partial Thromboplastin Time Blood Test
  • Penile Cancer
  • Peripheral T-Cell Lymphoma
  • Pernicious Anemia
  • Petechiae
  • Pituitary Cancer
  • Plasma Cell Dyscrasia
  • POEMS Syndrome
  • Polycythemia
  • Porphyria
  • Postthrombotic Syndrome
  • Primary Myelofibrosis
  • Primary Systemic Amyloidosis
  • Prolymphocytic Leukemia
  • Prostate Cancer
  • Protein C Deficiency
  • Protein S Deficiency
  • Prothrombin Gene Mutation
  • Pure Red Cell Aplasia
  • Purpura
  • Rectal Cancer
  • Recurrent Thrombosis
  • Red Blood Cell Disorders
  • Refractory Anemia With Excess Blasts
  • Rhabdomyosarcoma
  • Sarcoma
  • Secondary Polycythemia
  • Sezary Syndrome
  • Sickle Cell Diseases
  • Sinus Cancer
  • Skin Cancer
  • Small Cell Lung Cancer
  • Soft Tissue Sarcoma
  • Spinal Tumor
  • Splenic Sequestration
  • Splenomegaly
  • Squamous Cell Carcinoma of the Head and Neck
  • Stomach Cancer (Gastric Cancer)
  • Sweat Gland Carcinoma
  • Testicular Cancer
  • Thalassemias
  • Thoracic Cancer
  • Throat Cancer
  • Thrombocytopenia
  • Thrombocytosis
  • Thrombophilia
  • Thrombotic Disorders
  • Thrombotic Thrombocytopenic Purpura
  • Thyroid Cancer
  • Transformed Lymphoma
  • Transitional Cell Carcinoma
  • Urethral Cancer
  • Uterine Cancer
  • Vaginal Cancer
  • Vaginal Melanoma
  • Venous-Occlusive Crisis
  • Von Willebrand Disease
  • Vulvar Cancer
  • Waldenstrom Macroglobulinemia (WM)
  • White Blood Cell Disorders
Show All Expertise

Insurance Accepted

  • Aetna US Healthcare
  • Amerihealth Caritas
  • Amerihealth Caritas Medicare
  • Cigna
  • Cigna HealthSpring
  • Clover Health Plan
  • CVS Health
  • Devon Health Services (Americare)
  • eLAP Services
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthPartners Medicare
  • HealthSmart
  • Highmark Blue Shield
  • Homestead Smart Health Plans
  • Horizon Blue Cross Blue Shield of New Jersey
  • Humana / Choicecare
  • Independence Blue Cross (Keystone East)
  • Intergroup
  • Keystone First
  • Keystone First Medicare
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oxford Health Plan
  • PA Health and Wellness (Centene) Medicare
  • PA Medicaid
  • PA Medicare
  • Preferred Health Care/LGH
  • Provider Partners Health Plan
  • Rail Road Medicare / Palmetto GBA
  • Remedy Partners at Penn Medicine
  • Tricare
  • United Healthcare
  • UnitedHealthcare Community Plan
  • US Family Health Plan
  • Veterans Choice Program

Education and Training

Medical School: University of Pennsylvania School of Medicine
Residency: Brown University, Rhode Island Hospital
Fellowship: Hospital of the University of Pennsylvania

Memberships

American Society of Clinical Investigation, National Association of American Physicians, National Bill and Melinda Gates Foundation, External Scientific Advisory Board for, National Drexel University, External Scientific Advisory Committee for NIH UO1 Award (Irwin Chaiken, PI), Local External Scientific Advisory Committee, National External Scientific Advisory Committee, National Interurban Clinical Club, National Member, Scientific Advisory Board, National Member, Scientific Advisory Board, National National Institutes of Health, Vaccine Research Center, Board of Scientific Counselors, National Program Organizing Committee for Conference on Retroviruses and Opportunistic Infections, International

Hospital Affiliation

Dr. Hoxie is employed by Penn Medicine.

Hospital Privileges:

  • Hospital of the University of Pennsylvania: Has privileges to treat patients in the hospital.
  • Penn Presbyterian Medical Center: On the medical staff, but does not have privileges to treat patients in the hospital.

Research

Description of Research Expertise:

Research Interests
Viral and cellular aspects of HIV (human immunodeficiency virus) and SIV (simian immunodeficiency virus) entry into cells; HIV and SIV pathogenesis; mechanisms of viral resistance to the host immune response; neutralizing antibodies; gene therapy of HIV infection.

Key words: AIDS, CD4, chemokine receptors, HIV, SIV, envelope glycoproteins, viral entry, neutralization, vaccine, vaccines, pathogenesis

Description of Research
Research in Dr. Hoxie's lab is focused on identifying viral and cellular determinants that are relevant to the ability of HIV and SIV to infect cells and to evade host immune responses. Four specific areas of work include:

1. The role of the HIV/SIV cytoplasmic tail in pathogenesis. Dr. Hoxie's group has identified endocytosis signals in the cytoplasmic tails of HIV, SIV and FIV Env proteins that reduce Env expression on the surface of infected cells. Dr. Hoxie has proposed that these signals could be relevant in pathogenesis by enabling virus-producing cells to survive host anti-viral immune responses. He has shown in an SIV model that viruses with mutations in this domain are markedly attenuated in vivo and controllable by host immune responses. Ongoing studies are addressing the mechanism for this attenuation, the components of the host immune response that are involved, and defects in viral assembly that are believed to underlie this effect. Additional studies are focusing on translating this project to SHIV viruses containing an HIV-1 envelope to determine if analogous mutations in their cytoplasmic tails can also lead to broadly protective immunity.

2. Studies of CD4-independent isolates of HIV. Dr. Hoxie has described CD4-independent isolates of HIV-1 and HIV-2 that can infect cells using chemokine receptors without CD4. His lab has shown that the genetic basis for this phenotype results from mutations that expose the chemokine receptor binding site on gp120. Efforts are in progress to identify the structural basis for this effect and to use CD4-independent envelope glycoproteins as HIV vaccine candidates. In addition, novel simian immunodeficiency viruses have been generated that lack a CD4 binding site to explore the consequences of CD4 tropism on pathogenesis and host immune responses. Additional studies are focusing on translating this project to novel SHIV viruses containing an HIV-1 envelope for evaluation in nonhuman primates.

3. Producing modified HIV envelope glycoproteins for vaccine studies. This work is directed towards deriving HIV envelope glycoproteins that can elicit broadly neutralizing antibodies. Current approaches are deriving viruses lacking structures that are believed to shield the envelope from humoral immune responses.

4. Gene therapy approaches using a fusion inhibitory peptide from the HIV-1 gp41 envelope molecule conjugated to the human chemokine receptor CXCR4. Published studies have shown that this molecule is potent and broad inhibitor of HIV-1 entry. Studies in the Hoxie lab are focusing on understanding the mechanism for this effect and exploring ways in which viral resistance to this inhibitor can occur. The modified CXCR4 inhibitory protein (termed C34-CXCR4) is currently being evaluated in human trials and the Hoxie lab is currently assessing whether subjects receiving autologous T cells that express this protein, produce antibodies to the C34-CXCR4 protein).

Rotation Projects
-Structure function studies of envelope glycoproteins focusing on mechanisms of CD4 and chemokine receptor engagement.
Modulation of Envelope glycoproteins for the design of immunogens that can elicit broadly neutralizing antibodies.
-The role of the HIV/SIV cytoplasmic tail in pathogenesis.
-Studies evaluating mechanisms of neutralization sensitivity and resistance to antibodies.

Lab personnel:
Research Specialists:
Beth Haggarty
Josephine Romano

Students:
Son Nguyen

Research Investigator:
George Leslie

Selected Publications:

Nolan KM, Jordan AP, and Hoxie JA: Effects of partial deletions within the HIV-1 V3 loop on coreceptor tropism and sensitivity to entry inhibitors J. Virology 82 (2): 664-73,2008.

Lin G, Bertolotti-Ciarlet A, Haggarty B, Romano J, Nolan KM, Leslie GJ, Jordan AP, Huang CC, Kwong PD, Doms RW, Hoxie J: Replication-competent variants of human immunodeficiency virus type 2 lacking the V3 loop exhibit resistance to chemokine receptor antagonists J. Virology 81 (18): 9956-66,2007.

Laakso MM, Lee FH, Haggarty B, Agrawal C, Nolan KM, Biscone M, Romano J, Jordan AP, Leslie GJ, Meissner EG, Su L, Hoxie JA, Doms RW: V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies PLoS Pathogens 3 (8): e117,2007.

Fernando K, Hu H, Ni H, Hoxie JA, Weissman D: Vaccine-delivered HIV envelope inhibits CD4(+) T-cell activation, a mechanism for poor HIV vaccine responses Blood 9 (6): 2538-44,2007.

Byland R, Vance PJ, Hoxie JA, Marsh M: A conserved dileucine motif mediates clathrin and AP-2-dependent endocytosis of the HIV-1 envelope protein Mol. Biol Cell 18 (2): 414-25,2007.

Chaipan C, Soilleux EJ, Simpson P, Hofmann H, Gramberg T, Marzi A, Geier M, Stewart EA, Eisemann J, Steinkasserer A, Suzuki-Inoue K, Fuller GL, Pearce AC, Watson SP, Hoxie JA, Baribaud F, Pohlmann S: DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets J. Virology 80 (18): 8951-60,2006.

Wei Q, Stallworth JW, Vance PJ, Hoxie JA, Fultz PN: Simian immunodeficiency virus (SIV)/immunoglobulin G immune complexes in SIV-infected macaques block detection of CD16 but not cytolytic activity of natural killer cells Clin. Vaccine Immunology 13 (7): 768-78,2006.

View all publications

Academic Contact Info

522G Johnson Pavilion
3610 Hamilton Walk

Philadelphia, PA 19104
Phone: (215) 898-0261

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