University of Toledo Open Journal System

hussain, ashaq

Rawan Moussa

Mahasin Osman

The University of Toledo Translation Journal of Medical Sciences 
Dr. Lance D. Dworkin Department of Medicine Research Symposium           UTJMS 2025 June 30, 13(S3):e1-e1  
 
 
 
https://dx.doi.org/10.46570/utjms-2025-1402    ©2025 UTJMS 
  
 
Loss of IQGAP1 Lends Advantage to Female Mice 
Against Predisposition to Type 2 Diabetes 
Ashaq Hussain1, Rawan Moussa1, Mahasin Osman2* 
1Student, College of Medicine and Life Sciences, 3000 Arlington Avenue, The University of Toledo, Toledo OH 
43615 
2Associate Professor, Division of Hematology Oncology, Department of Medicine, 3000 Arlington Avenue, The 
University of Toledo, Toledo OH 43615 
Email: Mahasin.Osman@utoledo.edu 
Received: 2024-08-09 
Accepted: 2024-09-16 
Published: 2025-06-30 
Type 2 Diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia and elevated 
insulin resistance accompanied by low levels of insulin production in pancreatic β cells. Although sex 
differences in T2D manifestation have been recognized in human and animal models the molecular 
underpinning remains unclear. The scaffold signaling protein IQGAP1 has been implicated in insulin 
signaling and recycling and its mRNA is down regulated in humans with T2D. Here we report a female-
specific protective role of IQGAP1 in mice against predisposition to developing T2D. Our results show 
significant metabolic differences in male and female mice lacking iqgap1 gene (iqgap1-/-). We find that 
the loss of iqgap1 lends protection against obesity in male mice only under high fat diet (HFD) 
conditions. Compared to iqgap1-/- male mice, iqgap1-/- females exhibit significantly reduced body 
weight under both normal and HFD conditions. Measurements of physiological parameters revealed that 
iqgap1-/- females have increased insulin sensitivity and better plasma glucose clearance rate than their 
male counterparts. Analyses of the involved IQGAP1 pathway and organ site of action suggest 
involvement of ERα-IQGAP1-AMPKα signaling node in the pancreas. Further studies are underway to 
define how IQGAP1 executes his roles in this process differentially. 
Keywords: Diabetes, Pancreatic Beta Cell, Hyperglycemia, Insulin Resistance, Glucose Metabolism 
 
 
  


English

Loss of IQGAP1 Lends Advantage to Female Mice Against Predisposition to Type 2 Diabetes

Aljuneidi, Roaa

qafisheh, qutaiba

Sawaf, Bisher

Baniowda, Muath

Altorok, Nezam

The University of Toledo Translation Journal of Medical Sciences 
Dr. Lance D. Dworkin Department of Medicine Research Symposium  UTJMS 2025 June 30, 13(S3):e1-e2
                      
 
https://dx.doi.org/10.46570/utjms-2025-1417   ©2025 UTJMS 
  
 
Case Report: a unique course of severe 
Community-Acquired Methicillin-Resistant 
Staphylococcus Aureus (CA-MRSA) Cavitary 
Pneumonia with skipped phenomenon 
Roaa Aljuneidi1, Qutaiba Qafisheh2*, Bisher Sawaf1, Muath Baniowda1, Nezam Altorok3 
1Resident, Division of Internal Medicine, Department of Medicine, 3000 Arlington Avenue, The University of 
Toledo, Toledo OH 43615 
2College of Medicine and Life Sciences, 3000 Arlington Avenue, The University of Toledo, Toledo OH 43615 
3Professor, Program Director Rheumatology Fellowship, Director Internal Medicine Residency, Division of 
Internal Medicine, Department of Medicine, 3000 Arlington Avenue, The University of Toledo, Toledo OH 
43615 
Email: qqafish@rockets.utoledo.edu 
Received: 2024-08-16 
Accepted: 2024-09-16 
Published: 2025-06-30 
Community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) is a less common but 
increasingly recognized cause of severe pneumonia, particularly necrotizing pneumonia, in otherwise 
healthy individuals. The antibiotic resistance associated with CA-MRSA often leads to prolonged hospital 
stays and increased mortality. A unique feature of this pathogen, the "skipped phenomenon," is 
characterized by intermittent negative blood cultures and is linked to poor prognosis, complicating 
treatment decisions. We report the case of a 60-year-old male with a history of chronic obstructive 
pulmonary disease (COPD) and a significant smoking history, who presented with severe CA-MRSA 
cavitary pneumonia. Initially, the patient exhibited mild respiratory symptoms that rapidly progressed to 
severe pneumonia, confirmed by imaging studies showing cavitary lesions. Despite initial treatment with 
vancomycin, the patient experienced persistent MRSA bacteremia for more than 14 days, leading to the 
addition of ceftaroline to the therapeutic regimen. The patient's course was further complicated by the 
skipped phenomenon, with intermittent negative blood cultures followed by positive results, even as 
clinical symptoms began to improve. The skipped phenomenon, though rare, is a critical diagnostic 
challenge in the management of CA-MRSA infections, necessitating careful monitoring and repeated 
blood cultures to confirm bacterial clearance, as delayed or incomplete treatment can lead to severe 
complications. Our patient's presentation underscores the importance of considering CA-MRSA in cases 
of cavitary pneumonia, even in the absence of traditional risk factors, and highlights the potential 
The University of Toledo Translation Journal of Medical Sciences 
Dr. Lance D. Dworkin Department of Medicine Research Symposium  UTJMS 2025 June 30, 13(S3):e1-e2
                      
 
https://dx.doi.org/10.46570/utjms-2025-1417   ©2025 UTJMS 
  
 
benefits of combination antibiotic therapy in managing persistent bacteremia. This case emphasizes the 
need for high clinical suspicion for CA-MRSA pneumonia in patients with cavitary lung lesions, 
particularly in those with severe presentations. The presence of the skipped phenomenon requires 
vigilant monitoring to ensure complete bacterial eradication and successful patient outcomes. Early and 
aggressive treatment, guided by repeated cultures, is crucial in managing this life-threatening infection. 
Keywords: Sepsis, CA-MRSA, Community Acquired Pneumonia, Bacteremia 
 
 


Case Report: a unique course of severe Community-Acquired Methicillin-Resistant Staphylococcus Aureus (CA-MRSA) Cavitary Pneumonia with skipped phenomenon

Tiffany Yu

Michael Rice

Danyal Butt

Nathan Gilbert

Samantha Davis

Aya Abugharbyeh

The University of Toledo Translation Journal of Medical Sciences 
Dr. Lance D. Dworkin Department of Medicine Research Symposium UTJMS 2025 June 30, 13(S3):e1-e2                      
 
 
https://dx.doi.org/10.46570/utjms-2025-1435   ©2025 UTJMS 
  
 
Thromboangiitis Obliterans Presenting With 
Atypical Manifestation As Persistent 
Tenosynovitis Of The Wrist 
Tiffany Yu1*, Michael Rice1, Danyal Butt1, Nathan Gilbert2, Samantha Davis2, Aya Abugharbyeh2 
1College of Medicine and Life Sciences, 3000 Arlington Avenue, The University of Toledo, Toledo OH 43615 
2Fellow, Division of Gastroenterology, Department of Medicine, 3000 Arlington Avenue, The University of 
Toledo, Toledo OH 43615 
Email: tyu2@rockets.utoledo.edu 
Received: 2024-08-11 
Accepted: 2024-09-08 
Published: 2025-06-30 
Introduction: Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a rare inflammatory 
disease affecting approximately 0.02% of the population (1). Classically, it presents in young male 
smokers with distal extremity ischemia, ischemic digital ulcers, or digit gangrene (1).   
Case Presentation: A 49-year-old man with a past medical history positive for osteoarthritis, carpal 
tunnel, and a significant smoking history presented for pain and swelling of the right wrist and thumb. 
Along with TAO, sarcoidosis and rheumatoid arthritis were suspected due to elevated ACE and 
rheumatoid factor. His symptoms, however, were unresponsive to steroids. After excluding other 
inflammatory or autoimmune joint pain causes, a diagnosis of Buerger's disease was made from MRI 
which showed thrombophlebitis of the radial artery.  
Conclusion: This case underscores the need for clinicians to consider TAO in the differential diagnosis of 
vascular inflammation, especially in patients with a history of smoking, even in the absence of classic 
symptoms. TAO often presents with atypical manifestations, including thrombophlebitis and joint pain, 
which can complicate the diagnostic process. The rarity of TAO and its overlap with other inflammatory 
conditions make it crucial for healthcare providers to maintain a high index of suspicion. 
Keywords: Buerger's, Thromboangitis Obliterans, Tenosynovitis, Smoking, Vasculitis 
 
References 
1. Qaja E, Muco E, Hashmi MF. Buerger Disease. in: StatPearls [Internet]. 2023, Treasure Island (FL): 
StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430858/ 
The University of Toledo Translation Journal of Medical Sciences 
Dr. Lance D. Dworkin Department of Medicine Research Symposium UTJMS 2025 June 30, 13(S3):e1-e2                      
 
 
https://dx.doi.org/10.46570/utjms-2025-1435   ©2025 UTJMS 
  
 
2. Rivera-Chavarría IJ, Brenes-Gutiérrez JD. Thromboangiitis obliterans (Buerger's disease). Ann Med Surg 
(Lond), 2016. 7: p. 79-82. doi:10.1016/j.amsu.2016.03.028 
3. Khandekar, P., et al., Prognostic Factors in Buerger's Disease: A Review of Clinical Experience. Journal of 
Vascular Surgery, 2019. 70(4): p. 1231-1237. 
 


Thromboangiitis Obliterans Presenting With Atypical Manifestation As Persistent Tenosynovitis Of The Wrist

Faraz Zia

Sedlak, Jessica

Mohammad, Yusuf

Khan, Mohammad Zuhaib

Arefi, Isaac

Alkhas, Chmsalddin

Arshad, Azka

Vijendra, Divya

The University of Toledo Translation Journal of Medical Sciences 
Dr. Lance D. Dworkin Department of Medicine Research Symposium  UTJMS 2025 June 30, 13(S3):e1-e2
                      
 
https://dx.doi.org/ 10.46570/utjms-2025-1438   ©2025 UTJMS 
  
 
Wegener's Granulomatosis with Polyangiitis with 
Gynecological Manifestation 
Faraz Zia1*, Jessica Sedlak1, Yusuf Mohammad1, Mohammad Z. Khan1, Isaac Arefi1, Chmsalddin Alkhas1, Azka 
Arshad1, Divya Vijendra2 
1College of Medicine and Life Sciences, 3000 Arlington Avenue, The University of Toledo, Toledo OH 43615 
2Assistant Professor, Division of Hematology and Oncology, Department of Medicine,3000 Arlington Avenue, 
The University of Toledo, Toledo OH 43615 
Email: faraz.zia@rockets.utoledo.edu 
Received: 2024-08-01 
Accepted: 2024-09-08 
Published: 2025-06-30 
Introduction: Granulomatosis with Polyangiitis (GPA), previously known as Wegener’s Granulomatosis, is 
a potentially life-threatening autoimmune disorder. Systemic blood vessel inflammation in GPA can lead 
to granulomas causing symptoms including focal segmental glomerulonephritis, interstitial lung disease 
and common systemic vasculitis symptoms like sinus-bleeding. Diagnosing GPA can be challenging due to 
overlap with other diseases. Positive C-ANCA antibodies are sensitive blood-markers, which are followed 
by tissue biopsies that show inflammation with granulomatous changes and necrotizing vasculitis 
affecting small to medium-sized vessels.   
Case Presentation: A 59-year-old-female with a 4-year history of GPA had a novel presentation of severe 
progressing pelvic pain. Patient was sexually inactive since 2011 and denied dysuria, however, liquid-
contact to the perineum caused significant pain. Initial diagnosis was bacterial vaginosis and yeast. 
Shortly after beginning appropriate BV medicine regimen, moderate vaginal bleeding was observed, 
initially using 4-pads/day, progressing to spotting eventually. Endometrial ultrasound was not performed 
due to patient pain-intolerance and CT did not comment on endometrial thickness. GPA was in remission 
with the patient not on any treatment regimen at this time.   Vulvar biopsy was then performed 
confirming vulvar cellulitis and leukocytoclastic vasculitis after which antibiotics, norco and rituximab 
were initiated. Visual inspection showed a rectovaginal fistula however the surgeon did not attempt 
repair due to fear of complication and limited access. To prevent infection from bowel leakage, a 
colostomy bag was placed.       
Discussion/Conclusion: Gynecological complications of GPA are exceedingly rare with less than 1% of 
patients presenting with gynecological symptoms, most frequently bleeding. The cervix and vagina are 
the most commonly affected genital areas. GPA should be considered when biopsies of malignant-
appearing gynecological tissues are negative for malignancy. Treatment is effective and typically includes 
The University of Toledo Translation Journal of Medical Sciences 
Dr. Lance D. Dworkin Department of Medicine Research Symposium  UTJMS 2025 June 30, 13(S3):e1-e2
                      
 
https://dx.doi.org/ 10.46570/utjms-2025-1438   ©2025 UTJMS 
  
 
glucocorticoids and either cyclophosphamide, methotrexate, or azathioprine. Rituximab can also be used 
alone, as seen in this case study. 
Keywords: Wegeners, Granulomatosis with Polyangitis, Gynecology, Autoimmune Disorders 
 
References 
1. Pereira A, Magrina JF, Magtibay PM, Stamps BG, Muñoz-Nuñez E, Perez-Medina T. Granulomatosis 
with Polyangiitis-Mimicking Advanced Gynecological Cancer: A Case Report and Systematic Review of the 
Literature. J Pers Med, 2022 Feb 16. 12(2):289. doi:10.3390/jpm12020289 
2. Garlapati P, Rout P, Qurie A. Granulomatosis With Polyangiitis. [Updated 2024 Aug 31]. In: StatPearls 
[Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: 
https://www.ncbi.nlm.nih.gov/books/NBK557827/  


Wegener's Granulomatosis with Polyangiitis with Gynecological Manifestation

Starbuck, Hannah

Acharya, Aditya

Holtzapple, Zachary

Usman Ali, Muhammad

The University of Toledo Translation Journal of Medical Sciences 
Dr. Lance D. Dworkin Department of Medicine Research Symposium             UTJMS 2025 June 30, 13(S3):e1-e2  
 
 
 
https://dx.doi.org/10.46570/utjms-2025-1443   ©2025 UTJMS 
  
 
Straight to the Dome - Cefepime Induced 
Neurotoxicity 
Hannah Starbuck1*, Aditya Acharya1, Zachary Holtzapple2, Mohammad U. Ali3 
1College of Medicine and Life Sciences, 3000 Arlington Avenue, The University of Toledo, Toledo OH 43615 
2Resident, Division of Internal Medicine, Department of Medicine, 3000 Arlington Avenue, The University of 
Toledo, Toledo OH 43615 
3Assistant Professor, Division of Nephrology, Department of Medicine, 3000 Arlington Avenue, The University 
of Toledo, Toledo OH 43615 
Email: hannah.starbuck@rockets.utoledo.edu 
Received: 2024-08-01 
Accepted: 2024-09-09 
Published: 2025-06-30 
Introduction: The commonly used cephalosporin, Cefepime, has been reported to cause encephalopathy 
at an incidence rate of up to 14.3%. This neurotoxicity is highly dependent on route of administration, 
continuous versus intermittent dosing, renal function, and patient population (1-2).    
Case presentation: An 80-year-old male with no history of kidney disease presented to the emergency 
department as a stroke alert. The patient had a history of chronic back pain requiring multiple surgeries 
complicated by cerebral spinal fluid cultures growing Pseudomonas Aeruginosa. The patient was started 
on intravenous Cefepime one month prior to admission. Magnetic resonance imaging of the brain 
revealed no intracranial abnormalities nor signs of cerebral vascular accident. The patient was 
hemodynamically stable and noted to have stage 3 acute kidney injury. Electroencephalogram (EEG) 
revealed myoclonic seizure activity. The diagnosis of Cefepime induced neurotoxicity was made as the 
patient was on the standard dose of Cefepime in the setting of worsening renal function. The patient was 
transferred to the intensive care unit for emergent dialysis followed by continuous renal replacement 
therapy (CRRT). Subsequently, mental status continued to improve with resolution of seizure activity on 
EEG.   
Discussion: Cefepime induced neurotoxicity (CIN) should be considered a diagnosis of exclusion 
requiring high clinical suspicion and pertinent history. EEG findings are typically characterized by 
generalized periodic discharges with triphasic wave or nonconvulsive status epilepticus (3). Patients with 
impaired renal function are at an increased risk of CIN due to reduced clearance. Hemodialysis 
effectively removes Cefepime due to its pharmacologic properties including low protein binding and low 
The University of Toledo Translation Journal of Medical Sciences 
Dr. Lance D. Dworkin Department of Medicine Research Symposium             UTJMS 2025 June 30, 13(S3):e1-e2  
 
 
 
https://dx.doi.org/10.46570/utjms-2025-1443   ©2025 UTJMS 
  
 
molecular weight. The symptoms of CIN can last up to 2-3 days in patients with severe kidney injury 
without dialysis (4).  
Keywords: Cefepime, Neurotoxicity 
 
References 
1. Vercheval, C., Sadzot, B., Maes, N., Denooz, R., Damas, P., & Frippiat, F. Continuous infusion of 
cefepime and neurotoxicity: a retrospective cohort study. Clinical microbiology and infection : the 
official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2020 
Jul 9. S1198-743X(20)30386-4. Doi:10.1016/j.cmi.2020.07.003 
2. Payne, L. E., Gagnon, D. J., Riker, R. R., Seder, D. B., Glisic, E. K., Morris, J. G., & Fraser, G. L. 
Cefepime-induced neurotoxicity: a systematic review. Critical care (London, England), 2017. 
21(1): pp. 276. Doi:10.1186/s13054-017-1856-1 
3. Tamune, H., Hamamoto, Y., Aso, N., & Yamamoto, N. Cefepime-induced encephalopathy: Neural 
mass modeling of triphasic wave-like generalized periodic discharges with a high negative 
component (Tri-HNC). Psychiatry and clinical neurosciences, 2019. 73(1): pp. 34–42. 
Doi:10.1111/pcn.12795 
4. Lee, Se-Jin. Cefepime-induced neurotoxicity. Journal of Neurocritical Care, 2019. 2(12): pp. 74–
84.Doi:10.18700/jnc.190109 


Straight to the Dome - Cefepime Induced Neurotoxicity

Vento, Christopher (Gabby)

Andari, Elissar

The University of Toledo Translation Journal of Medical Sciences 
UTJMS 2025 October 15, 14(S1):e1-e2 doi:10.46570/utjms-2025-1486 
10.46570/utjms-2025-1486 ©2025 UTJMS 
Using iLINCS to mine for Oxytocin signature to 
find new drug candidates or molecular 
pathways that can be used for future 
treatment for autism 
Gabby (Chris) Vento1*, Elissar Andari2 
1College of Medicine and Life Sciences, 3000 Arlington Avenue, The University of Toledo, Toledo OH 43615 
2Assistant Professor, Department of Neurosciences and Psychiatry, 3000 Arlington Avenue, The University of 
Toledo, Toledo OH 43615 
Email: christopher.vento@rockets.utoledo.edu 
Received 12/4/2024 
Accepted: 12/18/2024 
Published 10/15/2025 
Introduction: There are currently no pharmacological treatments available to treat social affective symptoms 
in Autism. It has been proposed that the social-bonding hormone oxytocin could be administered to promote 
social affective ability in those with ASD 1–3.  The problem with simply administering Oxytocin as a 
neuropeptide is that its half-life is only around three minutes, thus greatly limiting its clinical usefulness 2. 
Identifying molecular pathways of oxytocin and mechanisms of action (MOA) of targets that are similar to 
oxytocin’s action, using transcriptomics available datasets, can be promising in identifying genes and pathways 
that could be further investigated in future translational autism research.    
Methods: Three RNA-SEQ studies were identified on the NCBI database that examined Oxytocin exposure to 
nerve cells in these data sets: GSE210528, GSE24666, and GSE199427, with the first two studies from rat tissue 
samples and the last one from human stem cells in a laboratory setting 4–6. The data was analyzed with the 
Library of Integrated Network-Based Cellular Signatures – or ILINCS, to find molecular pathways of oxytocin 
and mechanisms of action of genes that have similar transcriptomics signature to oxytocin. 
Results: Oxytocin had a significant effect on neural activity and signaling pathways, including enrichment of 
MAPK signaling. Oxytocin exposure led to positive regulation of protein phosphorylation and to Phosphatase 
Binding. Among the top concordant mechanisms of actions were shown to be HDAC Inhibitor, NF-kB Pathway 
Inhibitor, Dopamine Receptor and Serotonin Receptor Antagonist.  
Conclusion: This analysis indicates that Oxytocin does enrich molecular pathways, and has similar mechanisms 
of action to genes, that are directly involved in autism psychopathology. A combination of oxytocin and SSRIs 
or anti-inflammatory markers can be further investigated in laboratory settings under control conditions to 
better understand its mechanisms in the context of autism research.  
Keywords: Autism, ASD, Aspergers, Oxytocin, Psychoneuroendocrinology 
The University of Toledo Translation Journal of Medical Sciences 
UTJMS 2025 August 15, 14(S1):e1-e2 doi:10.46570/utjms-2025-1486 
10.46570/utjms-2025-1486 ©2025 UTJMS 
References 
1. Andari E, Duhamel JR, Zalla T, Herbrecht E,
Leboyer M, Sirigu A. Promoting social behavior
with oxytocin in high-functioning autism spectrum
disorders. Proc Natl Acad Sci U A, 2010. 107(9): pp.
4389-4394. doi:10.1073/pnas.0910249107
2. Guastella AJ, Hickie IB. Oxytocin Treatment,
Circuitry, and Autism: A Critical Review of the
Literature Placing Oxytocin Into the Autism
Context. Biol Psychiatry, 2016. 79(3):234-242.
doi:10.1016/j.biopsych.2015.06.028
3. Young LJ, Wang Z. The neurobiology of pair
bonding. Nat Neurosci, 2004. 7(10): pp. 1048-
1054. doi:10.1038/nn1327
4. Janz, P., Knoflach, F., Bleicher, K., Belli, S.,
Biemans, B., Schnider, P., Ebeling, M.,
Grundschober, C., & Benekareddy, M. Selective
oxytocin receptor activation prevents prefrontal
circuit dysfunction and social behavioral
alterations in response to chronic prefrontal cortex
activation in male rats. Front Cell Neurosci, 2023.
17: p. 1286552. doi:10.3389/fncel.2023.1286552
5. Nishimura H, Yoshimura M, Shimizu M, Sanada
K, Sonoda S, Nishimura K, Baba K, Ikeda N,
Motojima Y, Maruyama T, Nonaka Y, Baba R,
Onaka T, Horishita T, Morimoto H, Yoshida Y,
Kawasaki M, Sakai A, Muratani M, Conway-
Campbell B, Lightman S, Ueta Y. Endogenous
oxytocin exerts anti-nociceptive and anti-
inflammatory effects in rats. Commun Biol, 2022.
5(1): p.907. doi:10.1038/s42003-022-03879-8
6. Wasserman, A. H., Huang, A. R., Lewis-Israeli, Y.
R., Dooley, M. D., Mitchell, A. L., Venkatesan, M., &
Aguirre, A. Oxytocin promotes epicardial cell
activation and heart regeneration after cardiac
injury. Front Cell Dev Biol, 2022. 10: p.985298.
doi:10.3389/fcell.2022.985298
7. Xie, Z., Kropiwnicki, E., Wojciechowicz, M. L.,
Jagodnik, K. M., Shu, I., Bailey, A., Clarke, D. J. B.,
Jeon, M., Evangelista, J. E., V Kuleshov, M.,
Lachmann, A., Parigi, A. A., Sanchez, J. M., Jenkins,
S. L., & Ma'ayan, A. Getting Started with LINCS
Datasets and Tools. Curr Protoc, 2022. 2(7): p.
e487. doi:10.1002/cpz1.487


Using iLINCS to mine for Oxytocin signature to find new drug candidates or molecular pathways that can be used for future treatment for autism

Roshan Sirole

Ali Imami

Robert McCullumsmith

The University of Toledo Translation Journal of Medical Sciences 
UTJMS 2025 October 15, 14(S1):e1-e1 doi:10.46570/utjms-2025-1521 
10.46570/utjms-2025-1521 ©2025 UTJMS 
Identifying Repurposable Drugs for 
Schizophrenia using Transcriptomic Datasets
Roshan Sirole1, Ali Imami1, Robert E. McCullumsmith2* 
1College of Medicine and Life Sciences,  3000 Arlington Avenue, The University of Toledo, Toledo OH 43615 
2Professor, Chair of Department of Neurosciences and Psychiatry, 3000 Arlington Avenue, The University of 
Toledo, Toledo OH 43615 
Email: robert.mccullumsmith@utoledo.edu 
Received: 12/6/2024 
Accepted: 12/13/2024 
Published: 10/15/2025 
Background: Schizophrenia (SCZ) is a neuropsychiatric disorder that significantly affects cognition, behavior, 
and emotional regulation in approximately 0.45% of adults worldwide. Identification of effective treatment is 
critical to address the diverse and persistent symptoms of SCZ, particularly cognitive deficits and treatment-
resistant cases. 
Objectives: This study aims to identify repurposable drugs capable of reversing the dysregulated gene 
expression patterns associated with SCZ using a bioinformatics-driven approach, leveraging transcriptomic 
data from SCZ patient samples. 
Methods: Differential gene expression data from the PsychENCODE database were analyzed to identify SCZ-
specific molecular signatures. These were systematically compared to drug-induced transcriptomic profiles 
from public repositories. Utilizing the computational tool DrugFindR, candidate drugs with established safety 
profiles were prioritized for their potential to counteract SCZ-associated gene dysregulation. 
Results: The analysis identified multiple candidate drugs, including FDA-approved medications and those in 
clinical trials, with transcriptomic profiles discordant to SCZ-associated molecular changes. These drugs 
demonstrated the ability to reverse key dysregulated gene expression patterns, suggesting potential 
therapeutic benefits. Computational methodologies ensured an efficient, cost-effective approach, highlighting 
both validated and novel compounds that warrant further experimental exploration. 
Conclusion: This study underscores the potential of computational bioinformatics in drug repurposing for 
psychiatric disorders. By identifying drugs that target SCZ-associated gene dysregulation, we provide a 
promising avenue for precision medicine in SCZ treatment. The findings not only validate existing candidates 
but also introduce new therapeutic options that could significantly improve outcomes for patients with SCZ. 
Keywords: Schizophrenia, SCZ, Treatment-resistant Schizophrenia, Gene Dysregulation, Drug Repurposing 


Identifying Repurposable Drugs for Schizophrenia using Transcriptomic Datasets

Cuneo, Kayden

Ryan, William

Hanna, Sean

Imani, Ali

McCullumsmith, Robert

The University of Toledo Translation Journal of Medical Sciences 
UTJMS 2025 October 15, 14(S1):e1-e1 doi:10.46570/utjms-2025-1526 
10.46570/utjms-2025-1526 ©2025 UTJMS 
Exploring Phosphatase Targets in Alzheimer's 
Disease: A Comprehensive Sequence and 
Gene Expression Analysis
Kayden Cuneo1*, William G. Ryan, V2, Sean Hanna2, Ali Imami2, Robert E. McCullumsmith3 
1Lab Technician, Department of Neurosciences and Psychiatry, 3000 Arlington Avenue, The University of 
Toledo, Toledo OH 43615 
2College of Medicine and Life Sciences,  3000 Arlington Avenue, The University of Toledo, Toledo OH 43615 
3Professor, Chair of Department of Neurosciences and Psychiatry, 3000 Arlington Avenue, The University of 
Toledo, Toledo OH 43615 
Email: kayden.cuneo@utoledo.edu 
Received: 12/10/2024 
Accepted: 12/20/2024 
Published: 10/15/2025 
Background: Alzheimer's Disease (AD) is a complex, genetically heterogeneous neurodegenerative disorder 
and is the leading cause of age-related dementia. It primarily affects thinking, memory, and behavior, causing 
significant cognitive decline. Early diagnosis is crucial for improving care and reducing the disease's emotional 
and financial burden. Phosphatases play a key role in AD onset and progression, with protein phosphatases 
(PPs) linked to amyloid-beta plaque accumulation and neurofibrillary tangles (NFTs), hallmark features of AD. 
Reduced levels of PP1 and PP2A contribute significantly to AD. Identifying phosphatases involved in AD could 
offer new biomarkers for early diagnosis and therapeutic targets to halt or slow disease progression. 
Objective: This study aims to identify novel phosphatases implicated in AD, providing insights into their role in 
disease progression and potential targets for diagnosis and treatment. 
Methods: We conducted an extensive review of existing literature on phosphatase involvement in AD. Using 
PamGene chip technology, we identified phosphatase substrate sequences associated with AD. These 
sequences were analyzed through the NCBI BLAST tool to identify related genes. We then used the 
Kaleidoscope bioinformatics platform to cross-reference our findings with published studies, ensuring a 
comprehensive analysis of phosphatase involvement in AD. 
Results: Our initial analysis identified nine genes potentially involved in AD, supported by 26 related studies. 
Further data collection and analysis are ongoing, with plans to incorporate additional data sources and assess 
gene expression patterns in AD using the Kaleidoscope platform. 
Conclusion: Our findings highlight the need for further investigation into the role of phosphatases in AD. The 
initial data reveal a gap in the current understanding of how phosphatases influence AD progression. By 
identifying specific phosphatase targets, we hope to provide insights into potential therapeutic strategies and 
diagnostic tools for AD. 
Keywords: Alzheimer's Disease, Phosphatases


Exploring Phosphatase Targets in Alzheimer's Disease: A Comprehensive Sequence and Gene Expression Analysis

Chaudhary, Tanisha

Matson, Jyl

The University of Toledo Translation Journal of Medical Sciences 
UTJMS 2025 October 9, 14(S2):e1-e1 doi:10.46570/utjms-2025-1571 
10.46570/utjms-2025-1571 ©2025 UTJMS
Characterizing the role of SipA in Vibrio 
cholerae: Investigating the connection 
between SipA and other aspects of V. 
cholerae physiology
Tanisha Chaudhary1, Jyl Matson2* 
1College of Medicine and Life Sciences,  3000 Arlington Avenue, The University of Toledo, Toledo OH 43615 
2Associate Professor, Department of Medical Microbiology and Immunology, 3000 Arlington Avenue, The 
University of Toledo, Toledo OH 43615 
Email: jyl.matson@utoledo.edu 
Received: 1/3/2025 
Accepted: 2/14/2025 
Published: 10/9/2025 
Introduction: Stress response mechanisms are crucial for bacterial survival under varying environmental 
conditions. This study focuses on the highly conserved SipA protein in Vibrio cholerae, which is essential for 
stress tolerance and impacts bacterial physiology, including biofilm formation and carbon utilization. Despite 
significant preliminary findings, the regulatory mechanisms and functional roles of SipA remain poorly 
understood. 
Methods: In past studies we employed genetic and biochemical approaches, including mutant strain 
construction, survival and β-galactosidase assays, and advanced techniques like immunoprecipitation and 
mass spectrometry. Localization studies confirmed SipA’s cellular position, while regulatory pathways were 
investigated through transcriptomic analysis. Both Classical and El Tor biotypes of V. cholerae were studied to 
reveal biotype-specific roles of SipA. 
Results: Previous research established that SipA is regulated by a two-component system (VC1638-VC1639), 
which influences its expression in response to environmental stress, particularly the presence of antimicrobial 
peptides (AMPs). SipA plays a critical role in AMP resistance by interacting with the outer membrane protein 
OmpA, suggesting that they work together to facilitate AMP export and alleviate stress. This cooperative 
mechanism likely involves SipA aiding in the binding or transport of AMPs through OmpA, thereby reducing 
their toxic accumulation in the periplasm. To better understand how the two proteins relieve AMP stress, we 
are using ompA deletion strains and cellular fractionation assays to assess accumulation of AMPs in the 
periplasm. Additionally, we have observed that sipA-deficient strains exhibited increased biofilm production 
and growth defects on specific carbon sources, indicating its broader physiological roles beyond stress 
resistance. 
Conclusions: SipA is a multifaceted protein central to V. cholerae stress responses and physiology. Its role in 
AMP resistance highlights a conserved mechanism with potential applications in understanding bacterial stress 
survival strategies. 
Keywords: SipA, OmpA, Vibrio Cholera


Characterizing the role of SipA in Vibrio cholerae: Investigating the connection between SipA and other aspects of V. cholerae physiology.

Hegazi, Ahmad

Su, Kuo-Hui

Liu, Shi-He

The University of Toledo Translation Journal of Medical Sciences 
UTJMS 2025 October 9, 14(S2):e1-e1 doi:10.46570/utjms-2025-1573 
10.46570/utjms-2025-1573 ©2025 UTJMS
Role of heat shock factor 1 in nab-paclitaxel 
sensitization in pancreatic ductal 
adenocarcinoma 
Ahmad Hegazi1, Kuo-Hui Su2, Shi-He Liu3* 
1College of Medicine and Life Sciences,  3000 Arlington Avenue, The University of Toledo, Toledo OH 43615 
2Assistant Professor, Department of Cell and Cancer Biology, 3000 Arlington Avenue, The University of Toledo, 
Toledo OH 43615 
3Associate Professor, Department of Cell and Cancer Biology, 3000 Arlington Avenue, The University of Toledo, 
Toledo OH 43615 
Email: shi-he.liu@utoledo.edu 
Received: 1/3/2025 
Accepted: 2/14/2025 
Published: 10/9/2025 
Background: Pancreatic ductal adenocarcinoma (PDAC) is primarily treated with chemotherapy, with first-line 
options including gemcitabine, 5-fluorouracil, and nab-paclitaxel (NP). However, drug resistance is a frequent 
occurrence and poses a significant challenge. Heat shock factor 1 (HSF1) is a key regulator of the proteotoxic 
stress response (PSR), and this HSF1-mediated PSR promotes tumor survival and contributes to drug 
resistance. Despite these established roles, the impact of HSF1 on the reaction to antimicrotubule agents such 
as NP in PDAC remains unexplored. It has been reported that HSF1 prolongs mitotic arrest under the 
antimicrotubule agent nocodazole through delaying Cyclin B1 degradation in lung and bone cancer, a process 
key in increasing antimicrotubule cytotoxicity. The objective of this study is to determine whether HSF1 
modulates sensitivity to NP through prolonging NP-induced mitotic arrest in PDAC.  
Methods: Drug sensitivity (IC50) to NP was evaluated in PDAC cell lines (PANC-1, MIA PaCa-2, PDCL-5, HPAFII, 
and Capan-2) using CellTiter-Blue® Cell Viability Assay. Relative HSF1 protein expression levels were measured 
via immunoblotting. The level of Cyclin B1, cleaved PARP, and phosphorylated HSF1 at Ser326 were analyzed 
following NP treatment using immunoblotting. HSF1 was knocked down using siRNA or lentiviral shRNA and 
rescued with exogenous lentiviral Flag-HSF1 full-length plasmids. 
Results: In a panel of five human PDAC cell lines (PANC-1, MIA PaCa-2, PDCL-5, HPAFII, and Capan-2), relatively 
higher HSF1 expression was associated with reduced NP IC50 (p=0.008). NP IC50 was increased in PANC-1 cells 
following HSF1 siRNA knockdown. NP treatment induced HSF1 phosphorylation at Ser326, which correlated 
with Cyclin B1 expression and mitotic arrest at 12 hours in PANC-1 cells. 
Conclusion: PDAC cell lines with higher basal HSF1 expression exhibit greater sensitivity to NP. The following 
studies will validate these findings in vivo and investigate the detailed mechanism by which HSF1 regulates 
antimicrotubular-induced mitotic arrest in PDAC.   
Keywords: Pancreatic Cancer, Chemotherapy, Heat Shock Factor  1


Role of heat shock factor 1 in nab-paclitaxel sensitization in pancreatic ductal adenocarcinoma

Not a member yet