About

Michael L. Sikes is an Associate Professor and the Coordinator of the Molecular, Cellular and Developmental Biology Concentration within the Department of Biological Sciences at NC State University. He is based in Thomas Hall, and his contact information includes a phone number and email address. His research focuses on molecular and cellular biology, with a particular emphasis on gene expression responses to DNA damage, as evidenced by his publication on the knockdown of USF1 and USF2 and their effects on gene expression in cells subjected to DNA damage. His work also involves pharmacogenomics, immunology, microbiota, and bacterial virulence, contributing to the understanding of gene regulation, immune responses, and microbial physiology. Sikes has authored multiple scientific publications in reputable journals, indicating an active research program in these areas.

Research topics

• Medicine
• Computer Science
• Pathology
• Internal medicine
• Gastroenterology
• Mathematics education
• Pedagogy
• Radiology
• Psychology
• Biology
• Immunology

Selected publications

• Knockdown of USF1 and USF2 drives prolonged changes in the gene expression response of M12-5B3 cells to DNA damage

  PLoS ONE · 2025-07-14 · 1 citations

  articleOpen accessSenior author

  Therapeutic resistance remains a primary obstacle to curing cancer. Healthy cells exposed to genotoxic insult rapidly activate both p53-dependent and -independent non-genetic programs that pause the cell cycle and direct either DNA repair or apoptosis. Cancer cells exploit these same pathways as they respond to stresses induced by cancer therapies. In this study, we investigated a potential role for upstream stimulatory factor 1 (USF1) and USF2 in the p53-independent response of lymphoma cells to genotoxic therapy. We previously found that lymphocytes utilize the responsiveness of USF1 to double-stranded DNA breaks to coordinate T cell receptor beta (Tcrb) gene expression during V(D)J recombination. Here, microarray gene expression analysis of derivatives of the p53-deficient mouse B lymphoma cell line, M12, revealed that simultaneously depleting cells of both USF1 and USF2 altered the expression of 940 gene transcripts (>1.50-fold change, < 0.05 FDR), relative to cells expressing a scrambled control shRNA. Seven days after exposure to a single sublethal (5 Gy) dose of ionizing radiation, USF-depleted (USFKD) cells exhibited widespread and distinct transcriptional responses from those of irradiated controls (5035 and 5054 differentially expressed gene transcripts, respectively, with roughly half shared between both cell types). Gene ontology analyses revealed that USF knockdown induced numerous changes in the expression of genes critical for immune development and function while diminishing the responsiveness of genes linked to DNA damage pathways. Microarray findings were confirmed by RT-qPCR for a panel of genes responsive to USF knockdown and/or irradiation. These findings shed further light on transcriptional responses to ionizing radiation that manifest over time in transformed cells, identifying a novel p53-independent role in lymphocytic DNA damage stress responses for USF.

  PublisherDOI

• An Unusual Case of Intrahepatic Stone Masquerading as Cholangiocarcinoma

  ACG Case Reports Journal · 2025-02-01

  articleOpen access

  A cancer of the biliary tree, cholangiocarcinoma (CCA) often presents with painless jaundice, right upper quadrant abdominal pain, and unintended weight loss. Serologic testing to include cancer antigen 19-9 (CA 19-9) is elevated in CCA but can also be elevated in inflammatory processes in the biliary system. Diagnosis is difficult and even with advanced imaging techniques false-positives may occur. We present a case of a patient with elevated CA 19-9 and biliary stricture concerning for CCA but was due to hepatic stone. It demonstrates the challenge of correctly diagnosing CCA and an instance of nonmalignant elevation of CA 19-9.

  PublisherDOI

• S3934 Clinical Conundrum: Recurrent Delayed Immune Checkpoint Inhibitor-Induced Colitis or de novo Inflammatory Bowel Disease (IBD)?

  The American Journal of Gastroenterology · 2024-10-01 · 1 citations

  article
  PublisherDOI

• Adapting to the Rapidly Changing Landscape of Inflammatory Bowel Disease Management—An Opportunity to Medically Optimize Our Fighting Forces

  Military Medicine · 2024-07-06

  articleOpen access

  Disease Management-An Opportunity to Medically Optimize Our Fighting ForcesAs written, DoD instruction 6130.03,Volume 2 (DoDI 6130.03V2), service members (SM) with Inflammatory Bowel Disease (IBD), where the "condition requires immunomodulating or immunosuppressant medications," require referral to the Disability Evaluation System (DES).Our group, with tri-service and outside of contiguous United States representation, proposes an amendment allowing retention of SMs who transition to emerging Federal Drug Administration (FDA)-approved, oral, small molecule drugs (SMD).IBD is an autoimmune disorder encompassing both Crohn's disease (CD) and ulcerative colitis.The presentation ranges from severe inflammation with pain and hematochezia to a more indolent presentation with weight loss, stool changes, fatigue, malnutrition, and discomfort.Studies suggest increasing incidence of IBD over the past decade estimating that young adults (aged 20-29 years) have the highest incidence at 23 per 100,000.Notably, 65.9% of the active duty population is younger than 30 years of age and applying the incidence to this at-risk population suggests over 200 new diagnoses annually throughout the DoD.Typically, acute severe IBD flares necessitate hospitalization for administration of high-dose steroids, initiation of immunomodulatory medications, and potential surgery in refractory disease.Mild-to-moderate cases are managed in outpatient clinic with initiation of service compatible oral and/or topical 5-aminosalicyclic acid class of medications

  PublisherOA PDFDOI

• S3489 Rare Cause of the Common: Pancreatitis Secondary to Untreated Wilson’s Disease

  The American Journal of Gastroenterology · 2023

  • Medicine
  • Gastroenterology
  • Internal medicine

  Introduction: Wilson disease (WD) is a rare autosomal recessive disorder caused by ATP7B mutation leading increased cellular deposition of copper in multiple organs. Initial presentations of WD can range widely from acute liver failure to chronic decompensated cirrhosis and have neurologic manifestations. Including dystonia and Parkinson’s disease-like movements. We present a case of newly diagnosed WD which presented as recurrent acute pancreatitis (AP). Case Description/Methods: A 21-year-old previously healthy man presented with 3 months of chronic abdominal pain with initial lipase ranging from 384 to 2000 U/L and clinical presentation consistent with diagnosis of AP, albeit with normal cross-sectional imaging. Basic labs showed elevated liver enzymes. Imaging further revealed cirrhotic liver morphology with evidence of portal hypertension from venous collateralization and splenomegaly of unclear etiology. Diagnosis of WD established with Keyser Fleischer rings on slit lamp examination (Figure 1), undetectably low ceruloplasmin and 24-hour urinary copper of 367 mcg/24hr. Liver biopsy further confirmed WD with a hepatic copper concentration of 387.6 ug/g. On repeat liver ultrasound, it revealed cirrhosis with portal hypertension with hepatic venous pressure gradient of 14mmHg. Given the possibility of gallstone pancreatitis associated with WD, MRCP was performed and unremarkable. Furthermore, no alternative etiology of AP was discovered after workup for hypertriglyceridemia, alcohol/ingestion, autoimmune pancreatitis, and genetic syndromes were unremarkable. Supporting recurrent AP secondary to WD is resolution of episodes after several months trientine therapy, and recurrent episodes during periods of noncompliance. Discussion: We present a rare case of WD manifesting as recurrent pancreatitis, which to date has few reported cases in the literature, primarily associated with pigmented stone disease or copper deposition in the pancreas. After establishing the diagnosis, the temporal association of cessation of WD therapy followed by recurrent pancreatitis and clinical improvement with re-initiation of therapy favor copper deposition in pancreas as the key mechanism in pathogenesis. Given this association, we suggest that WD be considered in young patients with diagnosis of recurrent idiopathic pancreatitis. If discovered, we recommend early optimization of WD therapy which could prevent further episodes recurrent pancreatitis in this population.Figure 1.: Depiction of Kayser-Fleischer ring noted on the left cornea from copper deposition.

  PublisherDOI

• Pharmacogenomic Analyses Implicate B Cell Developmental Status and MKL1 as Determinants of Sensitivity toward Anti-CD20 Monoclonal Antibody Therapy

  Cells · 2023-06-07

  articleOpen access

  Monoclonal antibody (mAb) therapy directed against CD20 is an important tool in the treatment of B cell disorders. However, variable patient response and acquired resistance remain important clinical challenges. To identify genetic factors that may influence sensitivity to treatment, the cytotoxic activity of three CD20 mAbs: rituximab; ofatumumab; and obinutuzumab, were screened in high-throughput assays using 680 ethnically diverse lymphoblastoid cell lines (LCLs) followed by a pharmacogenomic assessment. GWAS analysis identified several novel gene candidates. The most significant SNP, rs58600101, in the gene MKL1 displayed ethnic stratification, with the variant being significantly more prevalent in the African cohort and resulting in reduced transcript levels as measured by qPCR. Functional validation of MKL1 by shRNA-mediated knockdown of MKL1 resulted in a more resistant phenotype. Gene expression analysis identified the developmentally associated TGFB1I1 as the most significant gene associated with sensitivity. qPCR among a panel of sensitive and resistant LCLs revealed immunoglobulin class-switching as well as differences in the expression of B cell activation markers. Flow cytometry showed heterogeneity within some cell lines relative to surface Ig isotype with a shift to more IgG+ cells among the resistant lines. Pretreatment with prednisolone could partly reverse the resistant phenotype. Results suggest that the efficacy of anti-CD20 mAb therapy may be influenced by B cell developmental status as well as polymorphism in the MKL1 gene. A clinical benefit may be achieved by pretreatment with corticosteroids such as prednisolone followed by mAb therapy.

  PublisherOA PDFDOI

• S2079 Cholangioscopy of IgG4 Sclerosing Cholangitis as Cholangiocarcinoma Mimic

  The American Journal of Gastroenterology · 2023

  1st authorCorresponding
  • Medicine
  • Radiology
  • Pathology

  Introduction: As a disease process first described in 2003, IgG4 related disease (IgG4-RD) and IgG4 sclerosing cholangitis is often difficult to diagnose. The American College of Rheumatology and European League Against Rheumatism developed a set of criteria for diagnosis of IgG4-RD, unique to location of pathology. Our patient met some of these criteria, though there was overlap with other diagnoses such as primary sclerosing cholangitis (PSC) and cholangiocarcinoma (CCA). Cholangioscopy and targeted intra-ductal biopsies is a relatively new in endoscopy and improves CCA yield. If CCA is not confirmed on biopsies, then IgG4-RD should be considered. With emerging data and groups working towards consensus diagnostic definitions, this case report highlights challenges encountered given the similarities with other disease entities. Case Description/Methods: We present a case of a 75-year-old male evaluated for obstructive jaundice with imaging findings concerning for likely CCA with mass-like enhancement of proximal left and right hepatic ducts extending to common hepatic duct. Endoscopic Retrograde Cholangiopancreatography (ERCP) demonstrated irregular stricture to bilateral hepatic ducts measuring 11mm in length. Despite concerning cholangioscopy findings of friable, nodular, and tortuous dilated vessels of the biliary wall mucosa, along with imaging findings, biopsies and brushings were negative for malignancy. A concurrent work up for IgG4-RD showed an IgG4 level of 146mg/dL. ERCP was repeated with direct ductal biopsy and endoscopic ultrasound (EUS) biopsy of adjacent lymph node, again negative for malignancy. Repeat cholangioscopy demonstrated improvement in ductal stricture and mucosal wall and IgG4 increased to 215. Patient was counseled and subsequently trialed on prednisone for diagnostic and therapeutic purposes. Follow up imaging demonstrated near complete resolution of mass like enhancement, 4 weeks after completion of steroid taper, favoring IgG4-SC over malignancy. Now greater than 1 year from initiation of work up, patient remains asymptomatic with normal IgG4 level and intrahepatic bile ducts on CT. Discussion: Our case highlights difficulty diagnosing IgG4-SC. Our patient had extensive malignancy workups that were negative. Ultimately serologies and steroids trial initiated for diagnostic and therapeutic purposes confirmed the diagnosis. Cholangioscopy for IgG-RD in the literature is very limited. Repeated cholangioscopy with improving findings not on steroids may increase suspicion for IgG-RD.

  PublisherDOI

• Pharmacogenomic Analyses Implicate B Cell Developmental Status and MKL1 as Determinants of Sensitivity toward Anti-CD20 Monoclonal Antibody Therapy

  UNC Libraries · 2023-07-07

  articleOpen access

  Monoclonal antibody (mAb) therapy directed against CD20 is an important tool in the treatment of B cell disorders. However, variable patient response and acquired resistance remain important clinical challenges. To identify genetic factors that may influence sensitivity to treatment, the cytotoxic activity of three CD20 mAbs: rituximab; ofatumumab; and obinutuzumab, were screened in high-throughput assays using 680 ethnically diverse lymphoblastoid cell lines (LCLs) followed by a pharmacogenomic assessment. GWAS analysis identified several novel gene candidates. The most significant SNP, rs58600101, in the gene MKL1 displayed ethnic stratification, with the variant being significantly more prevalent in the African cohort and resulting in reduced transcript levels as measured by qPCR. Functional validation of MKL1 by shRNA-mediated knockdown of MKL1 resulted in a more resistant phenotype. Gene expression analysis identified the developmentally associated TGFB1I1 as the most significant gene associated with sensitivity. qPCR among a panel of sensitive and resistant LCLs revealed immunoglobulin class-switching as well as differences in the expression of B cell activation markers. Flow cytometry showed heterogeneity within some cell lines relative to surface Ig isotype with a shift to more IgG+ cells among the resistant lines. Pretreatment with prednisolone could partly reverse the resistant phenotype. Results suggest that the efficacy of anti-CD20 mAb therapy may be influenced by B cell developmental status as well as polymorphism in the MKL1 gene. A clinical benefit may be achieved by pretreatment with corticosteroids such as prednisolone followed by mAb therapy.

  PublisherDOI

• Hands-on immunology: Engaging learners of all ages through tactile teaching tools

  Frontiers in Microbiology · 2022 · 5 citations

  • Computer Science
  • Mathematics education
  • Psychology

  operon molecular puzzle, we report here two TTT-GIL activities designed to engage diverse learners from middle schoolers to masters students in exploring molecular interactions within the immune system. By pairing physical models with structured activities built on the constructivist framework of Process-Oriented Guided Inquiry Learning (POGIL), TTT-GIL activities guide learners through their interaction with the model, using the Learning Cycle to facilitate construction of new concepts. Moreover, TTT-GIL activities are designed utilizing Universal Design for Learning (UDL) principles to include all learners through multiple means of engagement, representation, and action. The TTT-GIL activities reported here include a web-enhanced activity designed to teach concepts related to antibody-epitope binding and specificity to deaf and hard-of-hearing middle and high school students in a remote setting and a team-based activity that simulates the evolution of the Major Histocompatibility Complex (MHC) haplotype of a population exposed to pathogens. These activities incorporate TTT-GIL to engage learners in the exploration of fundamental immunology concepts and can be adapted for use with learners of different levels and educational backgrounds.

  PublisherDOI

• Sources of strain experienced by homegrown jihadist terrorists

  2017-01-01

  dissertation1st authorCorresponding
  Publisher

Recent grants

• NIH Grant R56AI070848

  NIH · $293k · 2010

• NIH Grant F32GM019597

  NIH · $30k

Frequent coauthors

• Eugene M. Oltz

  The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

  65 shared

• Leslie E. Huye

  Baylor College of Medicine

  49 shared

• John H.J. Petrini

  Memorial Sloan Kettering Cancer Center

  49 shared

• Michelle M. Le Beau

  49 shared

• David B. Roth

  University of Pittsburgh Medical Center

  49 shared

• Olga K. Mirzoeva

  UCSF Helen Diller Family Comprehensive Cancer Center

  49 shared

• Ruth Sullivan

  49 shared

• Carla F. Bender

  University of Wisconsin–Madison

  49 shared