Welcome to the CURE-KY Monthly Gathering 5/6/2026

Tentative Schedule�🕓 4:00–4:45 PM –

Arrive, grab food, and settle in�🧠 4:45–5:30 PM –

One-slide Lab Presentations on Emerging Diseases�💬 5:30–6:00 PM –

Network and Collaboration Planning

Presentation Order:

1. Dr. Reddy Palli – CAFÉ

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2. Dr. Hossam El-Sheikh Ali – CAFÉ

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3. Dr. Feng Li – CAFÉ

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4. Dr. Eric Rogier – CAFÉ

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5. Dr. Rebecca Dutch – CoM

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6. Dr. Joel Howard – CoM

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7. Dr. Amelia Pinto – CoM

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8. Dr. James Brien – CoM

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9. Dr. Ilhem Messaoudi – CoM

Rapid, cost effective and highly sensitive detection of Borrelia burgdorferi using RPA-CRISPR/Cas12a

Crude DNA

1. Template preparation

Purified DNA

Column purification

Lysis buffer

No incubation

Purified genomic DNA

Crude genomic DNA

RPA amplification

2. Isothermal amplification (RPA)

Room Temp

(30 ºC)

Body Temp

(37 ºC)

Thermomixer

heat (39 ºC)

Good

amplification

Good

amplification

Strong

amplification

Cas12a-crRNA complex

Specific crRNA

Cas12a

activation

Upon binding

target DNA

Single-stranded DNA

(ssDNA) probe

Fluorophore-Quencher

Neg

Pos

Fluorescence readout

15-30 min incubation

Cas12a

3. CRISPR/Cas12a

Fluorescence assay

Focal Mucoid / Nocardioform Placentitis

Introduction

• Unique form of equine placentitis
• First reported in Texas and Central Kentucky in mid-1980s.
• Episodic outbreaks in 1998, 1999, 2011, 2017, 2020, & 2023.
• Economic losses

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Ongoing Projects

Early and specific biomarker

(serum proteomics)

Mechanisms underlying placental inflammation

(Chorioallantois transcriptomic & proteomics)

Route of infection ???

• Amycolatopsis spp
• Crossiella equi.
• Streptomyces spp

?

Diagnosis

Pathogenesis

• Transabdominal ultrasonography
• Large uterus and a limited area to visualize
• Small or relatively far lesion; Could be missed

• Influenza C and D: Influenza C virus (ICV) is a ubiquitous pathogen in humans, while influenza D virus is a common respiratory virus in bovines.
• Spillover: both pathogen and antibody surveillances support that human ICV is undergoing active spillover to cattle. Spillover of cattle IDV to humans is only supported by serology.
• Immediate questions to be addresses
• Potential cross-reactivity between ICV and IDV in serology (HI).
• Bovine ICV and human IDV detection and isolation.

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• Seeking collaborators: clinical research, antibody depletion assay, epidemiology, immunology, virology, ecology, molecular systematics, bioinformatics, computational biology.

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Influenza C and D in the Human-Cattle Interface

UK-AVID/Feng Li

Can’t Eat that Anymore: The rise of alpha-gal syndrome (AGS) in Kentucky

Nonsense mutation in GGTA1 occurred in ancestor of catarrhines leading to non-production of α-1,3-galactosyl transferase enzyme and no glycoproteins/glycolipids containing galactose-α-1,3-galactose (α-gal)

Koike, et al. PNAS (2007)

All other non-catarrhine mammals produce α-gal

(but not birds, crustaceans or fish)

Products containing α-gal

Ggta1 KO mice

Tick feeding Adoptive cell transfer

‘Rescue’ of AGS symptoms

Dual KO mice

EXPERIMENTAL APPROACHES: AGS IMMUNOLOGY

Human circulating immune cells

AGS patients vs non-AGS Activation/differentiation markers Single-cell transcriptomics Circulating plasma cytokines

Mouse therapeutic mAbs

Dairy

Mammalian meat

Vaccines containing gelatin

UK Healthcare: 2021-2025

KY among highest in AGS cases

Thompson, et al. MMWR (2023)

AGS first described in US and Europe in 2009

Strong association between bites

from ticks containing α-gal and

human AGS allergy (IgE sensitization)

Wilson, et al. Allergy (2024)

The Dutch Laboratory: Emerging and Established Respiratory Viruses

The Henipaviruses: Paramyxoviruses with Pandemic Potential: Nipah, Hendra and Cedar Viruses

• Nipah virus and Hendra virus are BSL-4 pathogens.
• Our group has worked extensively on viral entry and assembly: Transfection experiments only – no virus!!
• We are currently part of NSF EpscoR grant, using Hendra virus-like particles (VLPs) to understand large-scale purification methods for vaccine development
• Cedar virus can be worked with in a BSL-2+ environment – we have done some work with this.

What about HMPV – is it an emerging virus?

HMPV, like RSV and HPIV-3 are established human pathogens – not emerging! We work with all of these in the lab.

Integrated Vector Management of Borrelia burgdorferi-infected Ixodes scapularis in Kentucky� � Joel Howard, MD

USA Lyme Disease Cases (CDC)

Kentucky Ixodes scapularis 2022 (Pasternak)

Seeking Collaborators for IVM:

• Entomopathogenic fungi
• Vector genetic manipulation (CRISPR)
• Field applications for UAVs
• Local Health Departments

West Nile Virus, Vaccination, and Metabolic Disease

One Health premise: metabolic disease may create a shared vulnerability to severe WNV disease and weaker vaccine protection.

Central question: Why is severe WNV disease more common in people and horses with MetS-associated comorbidities?

Clinical burden

• CNS disease in comorbid hosts

• Humans and mice are dead-end hosts

• KY 2025: 19 neuroinvasive cases, 1 death; 15+ horse cases

Vaccine clue

• Equine WNV vaccine exists

• Less effective in horses with EMS

Mechanistic gap

• MetS-associated immune dysfunction

• Cellular metabolism can alter viral infectivity

• Does MetS blunt vaccine-induced protection?

Metabolic disease

Immune dysfunction

Altered viral replication

Severe disease + reduced vaccine protection

Project goal: define how MetS changes WNV infectivity and identify strategies that protect metabolically vulnerable hosts.

Working Model

Human Clinical Trial to Novel Antigen to Pre-clinical Evaluation

Brien lab:

Nat Med

2020

NPJ

Vaccines

2026

Messaoudi Lab studies on Emerging Diseases

• Ongoing Projects
• Transcriptional response to VSV-based vaccines against filoviruses (Dr. Marzi, NIH)
• Transcriptional response to Powassan virus (POWV) virus-like-particle (POW-VLP) based vaccine adjuvanted with a novel synthetic Toll-like receptor 7/8 agonist (Dr. Hirsch, OHSU)

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• Technical Skills
• ELISA, ELISpot, Luminex
• Cellular phenotype by flow cytometry
• Bulk and single cell RNA Seq
• BCR and TCR repertoires

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messaoudilab.com