About

Kenneth Adler is associated with the College of Veterinary Medicine at NC State University. The page does not provide specific details about his research focus, background, or key contributions. Therefore, no further biographical information is available from the provided text.

Research topics

• Medicine
• Internal medicine
• Biology
• Chemistry
• Pathology
• Cancer research
• Anatomy
• Biochemistry
• Immunology
• Cell biology
• Pharmacology

Selected publications

• MARCKS protein is a potential target in a naturally occurring equine model of neutrophilic asthma

  Respiratory Research · 2025-04-02 · 1 citations

  articleOpen access

  BACKGROUND: Asthma is a chronic inflammatory airway disease that affects millions of people worldwide. Horses develop asthma spontaneously and serve as a relevant model for multiple phenotypes and endotypes of human asthma. In horses with equine asthma (EA), environmental organic dust triggers increased inflammatory cytokines, excess airway mucus, reversible bronchoconstriction, and airway inflammation. In horses with severe EA (sEA), lower airway inflammation is invariably neutrophilic, making sEA a potential model for severe neutrophilic asthma in humans. Alveolar macrophages (AM) and airway neutrophils contribute to lower airway inflammation and tissue damage through the release of cytokines and toxic mediators including reactive oxygen species. Previous work shows that the Myristoylated Alanine Rich C Kinase Substrate (MARCKS) protein is increased in activated macrophages and neutrophils and is an essential regulator of inflammatory functions in these cell types. We hypothesized that MARCKS protein would be increased in bronchoalveolar lavage (BAL) cells from horses with EA, and that in vitro inhibition of MARCKS with a specific inhibitor peptide known as MyristoylAted N-terminal Sequence (MANS), would diminish cytokine production and respiratory burst. METHODS: BAL cells from two populations of healthy and asthmatic horses were evaluated for cytology and MARCKS protein analysis. Isolated alveolar macrophages and peripheral blood neutrophils were stimulated with zymosan to evaluate MARCKS inhibition in cytokine secretion and respiratory burst. RESULTS: We found increased levels of normalized MARCKS protein in total BAL cells from horses with asthma compared to normal horses. MARCKS inhibition with the MANS peptide had no effect on zymosan-stimulated release of tumor necrosis factor alpha (TNFα) or interleukin-8 (IL-8) from alveolar macrophages but did attenuate zymosan-stimulated respiratory burst in both alveolar macrophages and peripheral blood neutrophils. CONCLUSIONS: These findings point to a possible role for MARCKS in the pathophysiology of neutrophilic equine asthma and support further investigation of MARCKS as a novel anti-inflammatory target for severe neutrophilic asthma.

  PublisherOA PDFDOI

• Peptide Inhibitors of MARCKS Suppress Endotoxin Induced Uveitis in Rats

  Journal of Ocular Pharmacology and Therapeutics · 2022-04-01 · 3 citations

  articleOpen access

  Purpose: To determine if inhibition of Myristoylated Alanine Rich C Kinase Substrate (MARCKS) protein, using novel MARCKS inhibitor peptides, will reduce the severity of endotoxin-induced uveitis (EIU) in rats. Methods: EIU was induced in Lewis rats using subcutaneous administration of lipopolysaccharide. In the first phase of the study, 3 different novel MARCKS inhibitor peptides that mimic the N-terminal region of MARCKS (BIO-11006, or lower molecular weight analogs BIO-91201 or BIO-91202; Biomarck Pharmaceuticals, Ltd., Newtown, PA) were administered intravitreally (IVT) at 50 and 100 μM. In the second phase, BIO-91201 was administered IVT at 10, 50, and 100 μM and topically at the 100 μM concentration. The efficacy of MARCKS inhibitor peptides was assessed by clinical examination using slit lamp biomicroscopy, optical coherence tomography (OCT) anterior chamber cell counts, histopathology, and aqueous humor cytokine analysis. Results: Clinical scores were significantly reduced 24 h following uveitis induction in the first phase of the study in the following treatment groups: BIO-11006 50 μM IVT and 100 μM IVT, BIO-91201 50 μM IVT, and BIO-91202 100 μM IVT ( P < 0.05). OCT anterior chamber cell counts were significantly reduced in the first phase of the study in all treatment groups ( P < 0.001). OCT anterior chamber cell counts and histopathology scores were significantly reduced in the second phase of the study in the BIO-91201 50 μM IVT group ( P < 0.05). No effect was seen with topical administration. Conclusion: MARCKS inhibitor peptides were effective in reducing the severity of ocular inflammation and cellular influx in EIU.

  PublisherOA PDFDOI

• Phosphorylation-dependent proteome of Marcks in ependyma during aging and behavioral homeostasis in the mouse forebrain

  GeroScience · 2022-01-24 · 4 citations

  articleOpen access
  PublisherOA PDFDOI

• Peptide Inhibitors of MARCKS Reverse Endotoxin Induced Uveitis in Rats

  Investigative Ophthalmology & Visual Science · 2021-06-21

  articleOpen access
  Publisher

• Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies

  UNC Libraries · 2020-04-22

  articleOpen access1st authorCorresponding

  BACKGROUND: Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality. METHODS: In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery. RESULTS: From one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days. CONCLUSION: Here, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

  PublisherDOI

• Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

  Nature Communications · 2020 · 432 citations

  • Medicine
  • Pathology
  • Cancer research

  Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis.

  PublisherOA PDFDOI

• An Inhaled MARCKS (Myristoylated Alanine-Rich C Kinase Substrate) - Inhibitory Drug, BIO-11006, Elicited a Statistically-Significant Result (p= 0.02) in Overall Response Rate (ORR) After 3 Months Compared to Standard of Care Chemotherapy in a Phase 2 Trial of Late Stage Non Small Cell Lung Cancer (NSCLC)

  2020 · 2 citations

  1st authorCorresponding
  • Pharmacology
  • Chemistry
  • Medicine
  PublisherOA PDFDOI

• Deconstruct Lung Regenerative Medicine: From Cell Therapy to Secretome and Exosomes

  2020-05-01

  articleOpen access
  PublisherOA PDFDOI

• A pre-investigational new drug study of lung spheroid cell therapy for treating pulmonary fibrosis

  Stem Cells Translational Medicine · 2020 · 21 citations

  • Medicine
  • Cancer research
  • Pathology

  human cells. Histological analysis revealed no evidence of tumorigenicity, increased local immunological activity in the lungs, or an increase in liver enzyme production. These data demonstrate the safety and efficacy of lung spheroid cells in their application as therapeutic agents for pulmonary fibrosis, as well as their potential for clinical translation.

  PublisherOA PDFDOI

• Inhalation of Lung Spheroid Cell-Secretome and Exosomes Promotes Therapeutic Lung Repair in Rodent Models of Pulmonary Fibrosis

  2019-05-01 · 2 citations

  article
  PublisherDOI

Recent grants

• A novel therapeutic approach for Acute Lung Injury/ARDS

  NIH · $202k · 2014–2015

• NIH Grant P50HL014212

  NIH · $7.0M · 1992

• NIH Grant R01HL036982

  NIH · $3.8M · 2004

• Mechanism of Oxidant-Induced Respiratory Mucin Secretion

  NIH · $4.0M · 1987–2014

• NIH Grant R01HL037636

  NIH · $286k · 1991

Frequent coauthors

• Linda D. Martin

  42 shared

• Nancy J. Akley

  37 shared

• Bernard M. Fischer

  34 shared

• Shijing Fang

  North Carolina State University

  32 shared

• Xiangdong Wang

  Zhongshan Hospital

  32 shared

• Joungjoa Park

  North Carolina State University

  31 shared

• Anne L. Crews

  North Carolina State University

  30 shared

• Janice A. Dye

  Environmental Protection Agency

  25 shared

Awards & honors

• MERIT Award from the National Heart, Lung, and Blood Institu…
• O. Max Gardner Award (2004)