Kenneth W Liechty
- Professor, Surgery
- Vice Chair, Research
- Division Chief, Pediatric Surgery
- Professor, Pediatrics
- Professor, Obstetrics and Gynecology
- Professor, Biomedical Engineering
- Member of the Graduate Faculty
Contact
- (520) 626-5555
- Arizona Health Sciences Center, Rm. 4410
- Tucson, AZ 85724
- kliechty@arizona.edu
Awards
- Wound Healing Society President
- The Wound Healing Society, Spring 2022
Interests
No activities entered.
Courses
2024-25 Courses
-
Honors Thesis
PSIO 498H (Fall 2024) -
Pediatric Surgery
SURG 848E (Fall 2024)
2023-24 Courses
-
Independent Study
SURG 899 (Fall 2023) -
Pediatric Surgery
SURG 848E (Fall 2023)
Scholarly Contributions
Journals/Publications
- Apte, A., Liechty, K. W., & Zgheib, C. (2023). Immunomodulatory biomaterials on chemokine signaling in wound healing. Frontiers in pharmacology, 14, 1084948.More infoNormal wound healing occurs through a careful orchestration of cytokine and chemokine signaling in response to injury. Chemokines are a small family of chemotactic cytokines that are secreted by immune cells in response to injury and are primarily responsible for recruiting appropriate immune cell types to injured tissue at the appropriate time. Dysregulation of chemokine signaling is suspected to contribute to delayed wound healing and chronic wounds in diseased states. Various biomaterials are being used in the development of new therapeutics for wound healing and our understanding of their effects on chemokine signaling is limited. It has been shown that modifications to the physiochemical properties of biomaterials can affect the body's immune reaction. Studying these effects on chemokine expression by various tissues and cell type can help us develop novel biomaterial therapies. In this review, we summarize the current research available on both natural and synthetic biomaterials and their effects on chemokine signaling in wound healing. In our investigation, we conclude that our knowledge of chemokines is still limited and that many in fact share both pro-inflammatory and anti-inflammatory properties. The predominance of either a pro-inflammatory or anti-inflammatory profile is mostly likely dependent on timing after injury and exposure to the biomaterial. More research is needed to better understand the interaction and contribution of biomaterials to chemokine activity in wound healing and their immunomodulatory effects.
- Gallagher, L. T., Lyttle, B. D., Meyers, M. L., Gien, J., Zaretsky, M. V., Galan, H. L., Behrendt, N., Liechty, K. W., & Derderian, S. C. (2023).
Fetal lung volumes measured by MRI predict pulmonary morbidity among infants with giant omphaloceles
. Prenatal Diagnosis, 43(12), 1514-1519. doi:10.1002/pd.6449 - Gallagher, L. T., Wright, C. J., Lehmann, T., Khailova, L., Zarate, M., Lyttle, B. D., Liechty, K. W., & Derderian, S. C. (2023). Angiogenic and Inflammatory microRNA Regulation in a Mouse Model of Fetal Growth Restriction. The Journal of surgical research, 292, 234-238.More infoFetal growth restriction (FGR) is associated with impaired angiogenesis and chronic inflammation. MicroRNAs (miRs) are short noncoding RNAs that regulate gene expression at the post-transcriptional level by targeting messenger RNA (mRNA) for degradation or by suppressing translation. We hypothesize that dysregulation of miR-15b, an antiangiogenic miR, and miR-146a, an anti-inflammatory miR, are associated with the FGR's pathogenesis.
- Lyttle, B. D., Vaughn, A. E., Bardill, J. R., Apte, A., Gallagher, L. T., Zgheib, C., & Liechty, K. W. (2023). Effects of microRNAs on angiogenesis in diabetic wounds. Frontiers in medicine, 10, 1140979.More infoDiabetes mellitus is a morbid condition affecting a growing number of the world population, and approximately one third of diabetic patients are afflicted with diabetic foot ulcers (DFU), which are chronic non-healing wounds that frequently progress to require amputation. The treatments currently used for DFU focus on reducing pressure on the wound, staving off infection, and maintaining a moist environment, but the impaired wound healing that occurs in diabetes is a constant obstacle that must be faced. Aberrant angiogenesis is a major contributor to poor wound healing in diabetes and surgical intervention is often necessary to establish peripheral blood flow necessary for healing wounds. Over recent years, microRNAs (miRNAs) have been implicated in the dysregulation of angiogenesis in multiple pathologies including diabetes. This review explores the pathways of angiogenesis that become dysregulated in diabetes, focusing on miRNAs that have been identified and the mechanisms by which they affect angiogenesis.
- Peddibhotla, S., Caples, K., Mehta, A., Chen, Q. Y., Hu, J., Idlett-Ali, S., Zhang, L., Zgheib, C., Xu, J., Liechty, K. W., & Malany, S. (2023). Triazolothiadiazine derivative positively modulates CXCR4 signaling and improves diabetic wound healing. Biochemical pharmacology, 216, 115764.More infoDevelopment of specific therapies that target and accelerate diabetic wound repair is an urgent need to alleviate pain and suffering and the huge socioeconomic burden of this debilitating disease. C-X-C Motif Chemokine Ligand 12 (CXCL12) also know an stromal cell-derived factor 1α (SDF-1α) is a chemokine that binds the CXC chemokine receptor type 4 (CXCR4) and activates downstream signaling resulting in recruitment of hematopoietic cells to locations of tissue injury and promotes tissue repair. In diabetes, low expression of CXCL12 correlates with impaired wound healing. Activation of CXCR4 receptor signaling with agonists or positive allosteric modulators (PAMs) provides a potential for small molecule therapeutic discovery and development. We recently reported high throughput screening and identification of the CXCR4 partial agonist UCUF-728, characterization of in vitro activity and reduced wound closure time in diabetic mice at 100 μM as a proof-of-concept study. We report here, the discovery of a second chemical scaffold demonstrating increased agonist potency and represented by thiadiazine derivative, UCUF-965. UCUF-965 is a potent partial agonist of β-arrestin recruitment in CXCR4 receptor overexpressing cell line. Furthermore, UCUF-965 potentiates the CXCL12 maximal response in cAMP signaling pathway, activates CXCL12 stimulated migration in lymphoblast cells and modulates the levels of specific microRNA involved in the complex wound repair process, specifically in mouse fibroblasts. Our results indicate that UCUF-965 acts as a PAM agonist of the CXCR4 receptor. Furthermore, UCUF-965 enhanced angiogenesis markers and reduced wound healing time by 36% at 10.0 μM in diabetic mice models compared to untreated control.
- Vaughn, A. E., Lehmann, T., Sul, C., Wallbank, A. M., Lyttle, B. D., Bardill, J., Burns, N., Apte, A., Nozik, E. S., Smith, B., Vohwinkel, C. U., Zgheib, C., & Liechty, K. W. (2023). CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury. Pharmaceutics, 15(9).More infoAcute respiratory distress syndrome (ARDS) has approximately 40% in-hospital mortality, and treatment is limited to supportive care. Pneumonia is the underlying etiology in many cases with unrestrained inflammation central to the pathophysiology. We have previously shown that CNP-miR146a, a radical scavenging cerium oxide nanoparticle (CNP) conjugated to the anti-inflammatory microRNA(miR)-146a, reduces bleomycin- and endotoxin-induced acute lung injury (ALI) by decreasing inflammation. We therefore hypothesized that CNP-miR146a would decrease inflammation in murine infectious ALI. Mice were injured with intratracheal (IT) MRSA or saline followed by treatment with IT CNP-miR146a or saline control. Twenty-four hours post-infection, bronchoalveolar lavage fluid (BALF) and whole lungs were analyzed for various markers of inflammation. Compared to controls, MRSA infection significantly increased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; < 0.05), BALF proinflammatory cytokines (IL-6, IL-8, TNFα, IL-1β; < 0.01), and inflammatory cell infiltrate ( = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; < 0.05), bronchoalveolar proinflammatory protein leak (IL-6, IL-8, TNFα; < 0.05), and inflammatory infiltrate ( = 0.01). CNP-miR146a decreases inflammation and improves alveolar-capillary barrier integrity in the MRSA-infected lung and has significant promise as a potential therapeutic for ARDS.
- Vaughn, A. E., Louiselle, A. E., Tong, S., Niemiec, S. M., Ahmad, S., Zaretsky, M., Galan, H. L., Behrendt, N., Wilkinson, C. C., O'Neill, B., Handler, M., Derderian, S. C., Mirsky, D. M., & Liechty, K. W. (2023). Early outcomes of a myofascial repair technique for fetal myelomeningocele. Journal of pediatric surgery, 58(1), 20-26.More infoFetal repair of myelomeningocele (MMC) and myeloschisis leads to improved neurologic outcomes compared to postnatal repair, but the effects of modifications in closure techniques have not been extensively studied. Previous work has suggested that a watertight repair is requisite for improvement in hindbrain herniation (HBH) and to decrease postnatal hydrocephalus (HCP). Our institution adopted the myofascial closure technique for open fetal MMC repair in July 2019, which we hypothesized would result in decreased need for patch closure, improved HBH, and decreased rate of surgically-treated HCP.
- Vaughn, A. E., Lyttle, B. D., Tran, W., Derderian, S. C., Liechty, K. W., & Gien, J. (2023). Surgical Necrotizing Enterocolitis - Can We Predict the Need for Gastrostomy Tube Placement?. The Journal of surgical research, 295, 168-174.More infoNecrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among extremely premature infants. Approximately 50% of cases progress to surgery, frequently resulting in resection of necrotic bowel and ostomy creation. Premature neonates are at risk for bronchopulmonary dysplasia and feeding failure; surgery in these patients is higher risk. We evaluated the incidence of gastrostomy tube (GT) placement after ostomy reversal in surgical NEC to define a subset of patients who would benefit from concurrent ostomy reversal and GT placement.
- Wallbank, A. M., Vaughn, A. E., Niemiec, S., Bilodeaux, J., Lehmann, T., Knudsen, L., Kolanthai, E., Seal, S., Zgheib, C., Nozik, E., Liechty, K. W., & Smith, B. J. (2023). CNP-miR146a improves outcomes in a two-hit acute- and ventilator-induced lung injury model. Nanomedicine : nanotechnology, biology, and medicine, 50, 102679.More infoAcute respiratory distress syndrome (ARDS) has high mortality (~40 %) and requires the lifesaving intervention of mechanical ventilation. A variety of systemic inflammatory insults can progress to ARDS, and the inflamed and injured lung is susceptible to ventilator-induced lung injury (VILI). Strategies to mitigate the inflammatory response while restoring pulmonary function are limited, thus we sought to determine if treatment with CNP-miR146a, a conjugate of novel free radical scavenging cerium oxide nanoparticles (CNP) to the anti-inflammatory microRNA (miR)-146a, would protect murine lungs from acute lung injury (ALI) induced with intratracheal endotoxin and subsequent VILI. Lung injury severity and treatment efficacy were evaluated via lung mechanical function, relative gene expression of inflammatory biomarkers, and lung morphometry (stereology). CNP-miR146a reduced the severity of ALI and slowed the progression of VILI, evidenced by improvements in inflammatory biomarkers, atelectasis, gas volumes in the parenchymal airspaces, and the stiffness of the pulmonary system.
Presentations
- Liechty, K. W. (2023, May). Regeneration in Response to Injury: Lessons Learned from the Fetus. University of Arizona Department of Surgery Research Day. Tucson, AZ: University of Arizona.More infoLecture
- Liechty, K. W. (2023, November). Regeneration in Response to Injury: Lessons Learned from the Fetus. CarePoint Health Organization.More infoLecture
- Liechty, K. W. (2023, November). Regeneration in Response to Injury: Lessons Learned from the Fetus. Skin Research Group of Canada 10th Annual Conference. Canada.More infoLecture
- Liechty, K. W. (2023, November). Regeneration in Response to Injury: Lessons Learned from the Fetus. Surgery Grand Rounds. Tucson, AZ: University of Arizona.More infoLecture
- Liechty, K. W. (2023, October). Regeneration in Response to Injury: Lessons Learned from the Fetus. Diabetic Wounds Treatment Consensus Panel. Connecticut: Yale University.More infoLecture
- Liechty, K. W. (2023, October). Regeneration in Response to Injury: Lessons Learned from the Fetus. Robert Christensen Lectureship. Utah: University of Utah.More infoLecture
Others
- Guthrie, E., Fortier, K., Liechty, K. W., & Price, N. (2023, August). Pediatric Surgical Antibiotic Preoperative Prophylaxis Guidelines for Elective Surgery.More infoGuideline to assist in choosing antibiotic prophylaxis for children undergoing elective procedures. Used by the Banner system.