About

Herbert Greenberg has served as a member of the violin faculty at the Peabody Conservatory since 1988, where he has also held roles as String Chair, Faculty Chair, and Coordinator of the Violin Department. He has performed throughout the world as a concertmaster, soloist, and chamber musician. Greenberg was concertmaster of the Aspen Festival Orchestra for 17 seasons and has served as guest concertmaster for numerous orchestras including the Houston, St. Louis, Oregon, San Diego, National Arts Orchestra of Canada, Japan Virtuosi, Prague, Hungarian State Opera, and Bergen Philharmonic orchestras. He was a member of the Minnesota Orchestra, associate concertmaster of the Pittsburgh Symphony, and served as concertmaster of the Baltimore Symphony Orchestra for twenty years. Greenberg has collaborated with many of the world's leading conductors, such as David Zinman, William Steinberg, Andre Previn, Alan Gilbert, Sergiu Comissiona, Leonard Slatkin, Gunther Herbig, and Hans Vonk, and was featured in Strauss' Ein Heldenleben during the inaugural concert at Baltimore's Meyerhoff Symphony Hall. An avid chamber musician, he was a founding member of the Previn-Greenberg-Williams Trio and the Baltimore String Quartet, collaborating with notable musicians including Isaac Stern, Pinchas Zukerman, William Primrose, and Yo-Yo Ma. Greenberg has performed over fifty concerti from Bach to John Adams and has led both the New Arts Ensemble of Taipei and the Singapore Symphony as violinist-conductor. He is also associated with the Defiant Requiem Foundation, serving as concertmaster and solo violinist, and has performed at Terezin, the site of the Theresienstadt Concentration Camp, to tell the story of life in the Terezin Ghetto. Greenberg has recorded for Sony, Telarc, Argo, and Delos, and plays on the Jean Becker Stradivarius, dated 1685.

Research topics

• Biology
• Virology
• Medicine
• Immunology
• Molecular biology

Selected publications

• Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus

  Mucosal Immunology · 2025-01-20 · 8 citations

  articleOpen access

  Dimeric IgA (dIgA) is the dominant antibody in many mucosal tissues. It is actively transported onto mucosal surfaces as secretory IgA (sIgA) which plays an integral role in protection against enteric pathogens, particularly in young children. Therapeutic strategies that deliver engineered, potently neutralizing antibodies directly into the infant intestine through breast milk could provide enhanced antimicrobial protection for neonates. Here, we developed a murine model of maternal protective transfer against human rotavirus (RV) using systemic administration of a dimeric IgA monoclonal antibody (mAb). First, we showed that systemically administered dIgA passively transferred into breast milk and the stomach of suckling pups in a dose-dependent manner. Next, we optimized the recombinant production of a potently RV-neutralizing, VP4-specific dIgA (mAb41) antibody. We then demonstrated that systemic administration of dIgA and IgG mAb41 in lactating dams conferred protection from RV-induced diarrhea in suckling pups, with dIgA resulting in lower diarrhea incidence from IgG. Systemic delivery of engineered antimicrobial dIgA mAbs should be considered as an effective strategy for sIgA delivery to the infant gastrointestinal tract via breast milk to increase protection against enteric pathogens.

  PublisherDOI

• Viroporin activity is necessary for intercellular calcium signals that contribute to viral pathogenesis

  Science Advances · 2025-01-17 · 14 citations

  articleOpen access

  Viruses engage in a variety of processes to subvert host defenses and create an environment amenable to replication. Here, using rotavirus as a prototype, we show that calcium conductance out of the endoplasmic reticulum by the virus encoded ion channel, NSP4 , induces intercellular calcium waves that extend beyond the infected cell and contribute to pathogenesis. Viruses that lack the ability to induce this signaling show diminished viral shedding and attenuated disease in a mouse model of rotavirus diarrhea. This implicates nonstructural protein 4 (NSP4) as a virulence factor and provides mechanistic insight into its mode of action. Critically, this signaling induces a transcriptional signature characteristic of interferon-independent innate immune activation, which is not observed in response to a mutant NSP4 that does not conduct calcium. This implicates calcium dysregulation as a means of pathogen recognition, a theme broadly applicable to calcium-altering pathogens beyond rotavirus.

  PublisherDOI

• Mutations of two amino acids in VP5 mediate the attenuation of human rotavirus vaccine: evidence from <i>in vitro</i> and <i>in vivo</i> studies

  Journal of Virology · 2025-10-08 · 1 citations

  articleOpen access

  ABSTRACT Various vaccines, like polio, measles, and rotavirus, have been developed by serial-passaging in cell culture. Live oral rotavirus vaccines have been shown to be generally safe, but mechanisms of attenuation are not known. We have used a new, entirely plasmid-based reverse genetics system to artificially generate the novel human rotavirus vaccine strain CDC-9 (G1P[8]) and analyze the effect of the mutations within the VP4 gene on adaptation in vitro and attenuation in vivo . We demonstrated that out of the 6 amino acid mutations that appeared after serial passaging in Vero cells, mutations of wild-type CDC-9 P11 at VP4 AA331 and AA385 each or in combination were associated with increased replication in vitro comparable to cell-culture adapted CDC-9 P45. Neonatal rats infected with the single AA331 or AA385 mutant had reduced viral shedding, comparable to cell-culture passaged CDC-9 P45. We observed additional reduced shedding in neonatal rats that were infected with combination mutants harboring mutations at position AA331_385_388, indicative of a slight additive effect. Our data indicate that mutations in the VP5* region of the VP4 gene, particularly at position AA331 and AA385, are the determining factor for in vitro replication adaptation and in vivo attenuation of a G1P[8] rotavirus vaccine. This information provides great potential for targeted mutation in rotavirus vaccine generation instead of labor-consuming serial passaging in cell culture. IMPORTANCE Live oral rotavirus vaccines have been developed through serial passaging in cell culture and found to be generally safe and efficacious in children. Live vaccines are also found to be associated with rare but severe adverse events, such as intussusception, in vaccinated children. Mechanisms for vaccine attenuation and adverse effects are unknown. We have developed a novel human rotavirus vaccine strain (CDC-9) and demonstrated several amino acid mutations in the VP4 gene of cell-passaged virus. In the present study, we identified two key amino acid mutations via reverse genetics technology in VP4 that mediated enhanced growth in cell culture, including a human intestinal cell line, reduced virus shedding, and downregulated inflammatory response in neonatal rats. This study is the first to identify the molecular signatures that define attenuation of human rotavirus vaccine and should help provide guidance for developing new generations of safe and effective vaccines.

  PublisherDOI

• Correction to: Therapeutics and Diagnostics Discovery

  2024-01-01

  book-chapterOpen access
  PublisherOA PDFDOI

• MYADM binds human parechovirus 1 and is essential for viral entry

  Nature Communications · 2024-04-24 · 12 citations

  articleOpen access

  Human parechoviruses (PeV-A) are increasingly being recognized as a cause of infection in neonates and young infants, leading to a spectrum of clinical manifestations ranging from mild gastrointestinal and respiratory illnesses to severe sepsis and meningitis. However, the host factors required for parechovirus entry and infection remain poorly characterized. Here, using genome-wide CRISPR/Cas9 loss-of-function screens, we identify myeloid-associated differentiation marker (MYADM) as a host factor essential for the entry of several human parechovirus genotypes including PeV-A1, PeV-A2 and PeV-A3. Genetic knockout of MYADM confers resistance to PeV-A infection in cell lines and in human gastrointestinal epithelial organoids. Using immunoprecipitation, we show that MYADM binds to PeV-A1 particles via its fourth extracellular loop, and we identify critical amino acid residues within the loop that mediate binding and infection. The demonstrated interaction between MYADM and PeV-A1, and its importance specifically for viral entry, suggest that MYADM is a virus receptor. Knockout of MYADM does not reduce PeV-A1 attachment to cells pointing to a role at the post-attachment stage. Our study suggests that MYADM is a multi-genotype receptor for human parechoviruses with potential as an antiviral target to combat disease associated with emerging parechoviruses.

  PublisherOA PDFDOI

• A Viral Protein 4-Based Trivalent Nanoparticle Vaccine Elicited High and Broad Immune Responses and Protective Immunity against the Predominant Rotaviruses

  ACS Nano · 2024-02-14 · 8 citations

  articleOpen access

  The current live rotavirus (RV) vaccines show reduced effectiveness in developing countries, calling for vaccine strategies with improved efficacy and safety. We generated pseudovirus nanoparticles (PVNPs) that display multiple ectodomains of RV viral protein 4 (VP4), named S-VP4e, as a nonreplicating RV vaccine candidate. The RV spike protein VP4s that bind host receptors and facilitate viral entry are excellent targets for vaccination. In this study, we developed scalable methods to produce three S-VP4e PVNPs, each displaying the VP4e antigens from one of the three predominant P[8], P[4], and P[6] human RVs (HRVs). These PVNPs were recognized by selected neutralizing VP4-specific monoclonal antibodies, bound glycan receptors, attached to permissive HT-29 cells, and underwent cleavage by trypsin between VP8* and VP5*. 3D PVNP models were constructed to understand their structural features. A trivalent PVNP vaccine containing the three S-VP4e PVNPs elicited high and well-balanced VP4e-specific antibody titers in mice directed against the three predominant HRV P types. The resulting antisera neutralized the three HRV prototypes at high titers; greater than 4-fold higher than the neutralizing responses induced by a trivalent vaccine consisting of the S60-VP8* PVNPs. Finally, the trivalent S-VP4e PVNP vaccine provided 90–100% protection against diarrhea caused by HRV challenge. Our data supports the trivalent S-VP4e PVNPs as a promising nonreplicating HRV vaccine candidate for parenteral delivery to circumvent the suboptimal immunization issues of all present live HRV vaccines. The established PVNP-permissive cell and PVNP-glycan binding assays will be instrumental for further investigating HRV–host cell interactions and neutralizing effects of VP4-specific antibodies and antivirals.

  PublisherOA PDFDOI

• Reverse Genetics of Murine Rotavirus: A Comparative Analysis of the Wild-Type and Cell-Culture-Adapted Murine Rotavirus VP4 in Replication and Virulence in Neonatal Mice

  Viruses · 2024-05-12 · 7 citations

  articleOpen accessCorresponding

  Small-animal models and reverse genetics systems are powerful tools for investigating the molecular mechanisms underlying viral replication, virulence, and interaction with the host immune response in vivo. Rotavirus (RV) causes acute gastroenteritis in many young animals and infants worldwide. Murine RV replicates efficiently in the intestines of inoculated suckling pups, causing diarrhea, and spreads efficiently to uninoculated littermates. Because RVs derived from human and other non-mouse animal species do not replicate efficiently in mice, murine RVs are uniquely useful in probing the viral and host determinants of efficient replication and pathogenesis in a species-matched mouse model. Previously, we established an optimized reverse genetics protocol for RV and successfully generated a murine-like RV rD6/2-2g strain that replicates well in both cultured cell lines and in the intestines of inoculated pups. However, rD6/2-2g possesses three out of eleven gene segments derived from simian RV strains, and these three heterologous segments may attenuate viral pathogenicity in vivo. Here, we rescued the first recombinant RV with all 11 gene segments of murine RV origin. Using this virus as a genetic background, we generated a panel of recombinant murine RVs with either N-terminal VP8* or C-terminal VP5* regions chimerized between a cell-culture-adapted murine ETD strain and a non-tissue-culture-adapted murine EW strain and compared the diarrhea rate and fecal RV shedding in pups. The recombinant viruses with VP5* domains derived from the murine EW strain showed slightly more fecal shedding than those with VP5* domains from the ETD strain. The newly characterized full-genome murine RV will be a useful tool for dissecting virus-host interactions and for studying the mechanism of pathogenesis in neonatal mice.

  PublisherOA PDFDOI

• Safety and immunogenicity of the intranasal H3N2 M2-deficient single-replication influenza vaccine alone or coadministered with an inactivated influenza vaccine (Fluzone High-Dose Quadrivalent) in adults aged 65–85 years in the USA: a multicentre, randomised, double-blind, double-dummy, phase 1b trial

  The Lancet Infectious Diseases · 2024-07-11 · 12 citations

  article
  PublisherDOI

• Development and validation of a VP7-specific EIA for determining the potency and stability of inactivated rotavirus vaccine

  Journal of Virological Methods · 2024-11-26 · 2 citations

  articleOpen access

  To determine the potency of the inactivated rotavirus vaccine (IRV), we developed an enzyme immunoassay (EIA) using a biotin-conjugated RV VP7-specific monoclonal antibody. RV VP7, a pivotal structural protein in the outer capsid layer, governs RV G genotypes and prompts host immune responses, including neutralizing antibodies. This EIA showed high specificity, good linearity, high precision, and high accuracy, with a low limit of detection (LOD) and a limit of quantitation (LOQ) of 0.037 µg/ml RV antigen. The EIA was evaluated and proved suitable for establishing the long-term stability of IRV drug substance (DS) and aluminum-formulated drug product (DP) when stored at −70±10°C and 5±3 °C, respectively. Our results support the use of this EIA to examine the stability and determine the potency, antigen dose, lot-to-lot consistency, and lot release of IRV products. This RV potency assay may serve as an alternative to in vivo potency tests, making it suitable for quality control tests of cGMP IRV lots in clinical trials. • Novel assays assessed the potency and stability of inactivated rotavirus vaccines. • Assays showed high sensitivity and consistency for different IRV lots. • Assays assessed IRV antigenicity under different stability programs. • Assays proved to be a useful tool for ensuring IRV quality and release.

  PublisherDOI

• Rhesus rotavirus NSP1 mediates extra-intestinal infection and is a contributing factor for biliary obstruction

  PLoS Pathogens · 2024-09-30 · 9 citations

  articleOpen access

  We previously demonstrated that in Ifnar1-/-Ifngr1-/- or Stat1-/- suckling mice lacking intact type I and type II interferon (IFN) signaling, rhesus rotavirus (RRV) infection causes a lethal disease with clinical manifestations similar to biliary atresia, including acholic stools, oily fur, growth retardation, and excess mortality. Elevated levels of viral RNA are detected in the bile ducts and liver of diseased pups together with severe inflammatory responses in these tissues. However, the viral determinants and the molecular mechanisms driving this process remain incompletely understood. Using an optimized rotavirus (RV) reverse genetics system, we generated a panel of recombinant RVs that encode non-structural protein 1 (NSP1) derived from different RV strains. We found that compared to the parental simian SA11 strain that is less biliary pathogenic, SA11 containing an RRV-derived NSP1 resulted in severe biliary obstructive disease comparable to that associated with RRV infection, reflected by high levels of viral RNA and inflammation in the biliary tract, liver, and pancreas. In contrast, RRV containing an SA11-originated NSP1 showed only mild biliary obstruction comparable to what was observed during SA11 infection. Infection with a monoreassortant RRV virus carrying NSP1 from the bovine RV UK strain also showed substantially reduced viral replication in extra-intestinal organs and did not develop clinical biliary diseases. Mechanistically, RRV NSP1 seemed to promote active viral replication in hepatocytes and this expanded tropism led to enhanced infiltration of CD4 and CD8 T cells, causing immunopathology and damage in the hepatobiliary system. These results highlight an unexpectedly important role of RV NSP1 in viral replication and disease progression in extra-intestinal tissues.

  PublisherDOI

Recent grants

• Administrative Core

  NIH · $92.6M · 2003–2029

• NIH Grant UL1RR025744

  NIH · $44.1M · 2013

• NIH Grant R03TW005647

  NIH · $228k · 2007

• NIH Grant R01AI021362

  NIH · $6.6M · 2015

• NIH Grant R56AI021362

  NIH · $506k · 2017

Frequent coauthors

• Albert Z. Kapikian

  207 shared

• Ningguo Feng

  Stanford University

  199 shared

• Siyuan Ding

  Wellcome/Cancer Research UK Gurdon Institute

  119 shared

• Lyndon S. Oshiro

  111 shared

• Xiaosong He

  Guangzhou Medical University

  100 shared

• R. Bradley Sack

  86 shared

• John G. Bartlett

  Springer Nature (Germany)

  82 shared

• Kaarel T. Kaljot

  St. Luke's-Roosevelt Hospital Center

  82 shared

Education

• Gastroenterology Fellow

  Stanford University School of Medicine

  1976

• Intern and Resident (Medicine)

  Bellevue Hospital Center

  1972

• Bachelor of Arts

  Dartmouth College

  1966