Alexander Lemenze

Rutgers New Jersey Medical School | UMDNJ · Department of Pathology and Laboratory Medicine

The mammalian cerebral cortex is composed of a rich diversity of cell types. Sensory cortical cells are organized into networks that rely on their functional diversity to ultimately carry out a variety of sophisticated cognitive functions for perception, learning, and memory. The auditory cortex (AC) has been most extensively studied for its experi...

Resistance to KRAS therapy in pancreatic ductal adenocarcinoma (PDAC) involves cellular plasticity, particularly the epithelial-to-mesenchymal transition (EMT), which poses challenges for effective targeting. Chronic pancreatitis, a known risk factor for PDAC, elevates TGFβ levels in the tumor microenvironment (TME), promoting resistance to KRAS th...

Staphylococcus aureus is a versatile bacterium responsible for conditions ranging from mild skin and soft-tissue infections to serious disorders such as pneumonia and sepsis. Monocytes play a role in protection against pathogens by migrating to inflamed tissues and differentiating into macrophages but their specific role in the context of S. aureus...

Fungal pathogens are underappreciated causes of significant morbidity and mortality worldwide. In previous studies, we determined that a heat-killed, Cryptococcus neoformans fbp1-deficient strain (HK-fbp1) is a potent vaccine candidate. We determined that vaccination with HK-fbp1 confers protective immunity against lethal Cryptococcosis in an inter...

Natural history and mechanisms for persistent cognitive symptoms (“brain fog”) following acute and often mild COVID-19 are unknown. In a large prospective cohort of people who underwent testing a median of 9 months after acute COVID-19 in the New York City/New Jersey area, we found that cognitive dysfunction is common; is not influenced by mood, fa...

The mammalian cerebral cortex is composed of a rich diversity of cell types. Cortical cells are organized into networks that rely on their functional diversity to ultimately carry out a variety of sophisticated cognitive functions. To investigate the breadth of transcriptional diverse cell types in the sensory cortex, we have used single-nucleus RN...

Interferon ε (IFNε) is a unique type I IFN that has been implicated in host defense against sexually transmitted infections (STIs). Zika virus (ZIKV), an emerging pathogen, can infect the female reproductive tract (FRT) and cause devastating diseases, particularly in pregnant women. How IFNε contributes to protection against ZIKV infection in vivo...

In brief Endometrial stromal cell motility is fundamental to regeneration and repair of this tissue and crucial for successful reproduction. This paper shows a role for the mesenchymal stem cell (MSC) secretome in enhancing endometrial stromal cell motility. Abstract Cyclic regeneration and repair of the endometrium are crucial for successful repr...

Lupus is a systemic autoimmune disease characterized by the presence of autoantibodies that form immune complexes in tissues leading to the recruitment of immune cells and subsequent inflammation and organ damage. The origin of autoantibody-secreting B cells is not clear, but the germinal center (GC) is of particular interest as the B cells here un...

Transgender people are at greater risk than cisgender people of acquiring HIV and other sexually transmitted infections. Globally, the risk of acquiring HIV infection is nearly 49 times higher in transgender women than in other populations. Although behavioral and psychosocial factors contribute to the higher HIV risk in transgender people, gender-...

Interferon ε (IFNε) is a unique type I IFN that has been implicated in host defense against sexually transmitted infections (STIs). Zika virus (ZIKV), an emerging pathogen, can infect the female reproductive tract (FRT) and cause devastating diseases, particularly in pregnant women. How IFNε contributes to protection against ZIKV infection in vivo...

Tissue-resident memory T cells (Trms) are an important subset of lymphocytes that are lodged within non-lymphoid tissues and carry out diverse functions to control local pathogen replication and prevent dissemination. CD103 has been used to broadly define subsets of Trm cells within the intestine, with CD103+ and CD103- Trms having unique transcrip...

Ovarian stimulation (OS), utilized for the development of multiple ovarian follicles for IVF, induces supraphysiologic levels of E2 and an early rise in P4 that disrupt endometrial differentiation and decreases implantation rates or result in placental insufficiency and pregnancy complications. To improve pregnancy rates and reduce the risk of preg...

Introduction The acquisition of a metastatic phenotype is the critical event that determines patient survival from breast cancer. Several receptor tyrosine kinases have functions both in promoting and inhibiting metastasis in breast tumors. Although the insulin-like growth factor 1 receptor (IGF1R) has been considered a target for inhibition in bre...

H37Rv is the most widely used Mycobacterium tuberculosis strain, and its genome is globally used as the M. tuberculosis reference sequence. Here, we present Bact-Builder, a pipeline that uses consensus building to generate complete and accurate bacterial genome sequences and apply it to three independently cultured and sequenced H37Rv aliquots of a...

Introduction: Cyclic regeneration of the endometrium, and its repair after parturition or injury, are crucial for successful reproduction. Mesenchymal stem cells (MSCs) derived from bone marrow (BM-MSC) and umbilical cord (UC-MSC) facilitate tissue repair via their secretome, which contains growth factors and cytokines that promote wound healing. D...

Tissue-resident memory T (TRM) cells remain poised in the tissue and mediate robust protection from secondary infection. TRM cells within the intestine and other tissues are heterogeneous in their phenotype and function; however, the contributions of these TRM subsets to secondary infection remain poorly defined. To address the plasticity of intest...

Current scoring systems accurately predict risk of pre-liver transplant (LT) mortality but fall short in estimation of post-LT survival. This study seeks to identify biomarkers of pre-LT immune dysfunction that predict mortality following LT. From 10/1/13-3/23/21, 279 cirrhotic patients underwent assessment of plasma biomarker (Luminex) and clinica...

Background and Aims Current scoring systems accurately predict risk of pre-liver transplant (LT) mortality but fall short in estimation of post-LT survival. This study seeks to identify biomarkers of pre-LT immune dysfunction that predict mortality following LT. Methods From 10/1/13 − 3/23/21, 279 cirrhotic patients underwent assessment of plasma b...

Intestinal helminth parasites express excretory/secretory (ES) molecules, which modulate the type-2 immune response including anti-inflammatory and tissue repair pathways. TGF-β mimic (TGM), an ES molecule secreted by Heligmosomoides polygyrus (Hp), binds TGF-β receptors yet lacks structural homology to TGF-β and exhibits distinct receptor interact...

Neuroimmune interactions are crucial for regulating immunity and inflammation. Recent studies have revealed that the central nervous system (CNS) senses peripheral inflammation and responds by releasing molecules that limit immune cell activation, thereby promoting tolerance and tissue integrity. However, the extent to which this is a bidirectional...

Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A2B adenosine receptor (A2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blo...

Objectives: The Notch signaling pathway is evolutionarily conserved and has been implicated as a potential therapeutic target in several cancers. Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer with poor survival, higher prevalence in Black women than White women, and few effective adjuvant therapies. The objective of this study was t...

H37Rv is the most widely used M. tuberculosis strain. Its genome is globally used as the M. tuberculosis reference sequence. We developed Bact-Builder, a pipeline that leverages consensus building to generate complete and highly accurate gap-closed bacterial genomes and applied it to three independently sequenced cultures of a parental H37Rv labora...

Rickettsia is a genus of Gram-negative bacteria that has for centuries caused large-scale morbidity and mortality. In recent years, the resurgence of rickettsial diseases as a major cause of pyrexias of unknown origin, bioterrorism concerns, vector movement, and concerns over drug resistance is driving a need to identify novel treatments for these...

Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) serve as a first line of defense against luminal microbes. Although the presence of an intact microbiota is dispensable for γδ IEL development, several microbial factors contribute to the maintenance of this sentinel population. However, whether specific commensals influence po...

Through a multitude of studies, the gut microbiota has been recognized as a significant influencer of both homeostasis and pathophysiology. Certain microbial taxa can even affect treatments such as cancer immunotherapies, including the immune checkpoint blockade. These taxa can impact such processes both individually as well as collectively through...

Tbet⁺CD11c⁺ B cells arise during type 1 pathogen challenge, aging, and autoimmunity in mice and humans. Here, we examined the developmental requirements of this B cell subset. In acute infection, T follicular helper (Tfh) cells, but not Th1 cells, drove Tbet⁺CD11c⁺ B cell generation through proximal delivery of help. Tbet⁺CD11c⁺ B cells developed p...

Macrophages are known to mediate anti-helminth responses, but it remains uncertain which subsets are involved or how macrophages actually kill helminths. Here, we show rapid monocyte recruitment to the lung after infection with the nematode parasite Nippostrongylus brasiliensis. In this inflamed tissue microenvironment, these monocytes differentiat...

Background & Aims Excessive shedding of apoptotic enterocytes into the intestinal lumen is observed in inflammatory bowel disease and is correlated with disease relapse. Based on their cytolytic capacity and surveillance behavior, we investigated whether intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) are actively involved i...

The acquisition of a metastatic phenotype is the critical event that determines patient survival from breast cancer. Several receptor tyrosine kinases have functions both in promoting and inhibiting metastasis in breast tumors. Although the insulin-like growth factor 1 receptor (IGF-1R) has been considered a target for inhibition in breast cancer,...

Logging road development is considered as potentially more damaging to a tropical forest than the felling of the actual trees. However, little work has been conducted to determine how logging road development impacts the soil microbial communities and associated C and N cycle activities in tropical forests. This study was conducted within an upland...

Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) serve as a first line of defense against luminal microbes. Although the presence of an intact microbiota is dispensable for γδ IEL development, several microbial factors contribute to the maintenance of this sentinel population. However, whether specific commensals influence po...

Animal models that recapitulate human diseases and disorders are widely used to investigate etiology, diagnosis, and treatment of those conditions in people. Disorders during pregnancy are particularly difficult to explore as interventions in pregnant women are not easily performed. Therefore, models that allow for pre-conception investigations are...

Historically, IGF-1R has been considered a target for inhibition to treat breast cancer patients. We recently identified low levels of IGF-1R are associated with worse overall patient survival and basal-like, triple-negative breast cancer. Our findings present a frame-shift for the function of IGF-1R in breast cancer. To elucidate how loss of IGF-1...

Although, IGF-1R historically has been considered a target for inhibition to treat breast cancer patients, recently, we have identified low levels of IGF-1R are associated with worse overall patient survival and basal-like, triple-negative breast cancer (TNBC). Our findings present a frame-shift for the function of IGF-1R in breast cancer. To eluci...

Intestinal nematode infections trigger potent type 2 immune responses, although the mechanisms that initiate these host protective responses against multicellular parasites remain uncertain. We have previously reported that A2BAR deficient mice (A2BAR−/−) have an impaired type 2 immune response and delayed helminth expulsion during Heligmosomoides...

In the 1st trimester of human pregnancy, low oxygen tension or hypoxia, is essential for proper placentation and placenta function. Low oxygen levels and activation of signaling pathways have been implicated as critical mediators in the promotion of trophoblast differentiation, migration, and invasion with inappropriate changes in oxygen tension an...

Objective To assess the role of STAT4 activation in driving pathogenic follicular helper T (Tfh) cell secretion of the cytokines interleukin‐21 (IL‐21) and interferon‐γ (IFNγ) in murine and human lupus. Methods The effect of STAT4‐dependent Tfh cell signaling on cytokine production and autoreactive B cell maturation was assessed temporally during...

Multicellular intestinal nematode parasites can cross the epithelial barrier potentially causing tissue damage and release of danger associated molecular patterns (DAMPs) that may promote type 2 responses and host protective immunity. We investigated whether adenosine specifically binding the A2B adenosine receptor (A2BAR) on epithelial cells playe...

Mutations in Integral membrane protein 2B (ITM2b/BRI2) gene causes familial British and Danish dementia (FBD and FDD), autosomal dominant disorders characterized by progressive cognitive deterioration. Two pathogenic mechanisms, which may not be mutually exclusive, have been proposed for FDD and FBD: 1) loss of BRI2 function; 2) accumulation of amy...

Inga edulis and Pentaclethra macroloba are dominant N-fixing forest trees in Costa Rica, likely important for recovery of soil N and C after deforestation, yet little is known of their soil microbiomes nor how land use impacts them. Soils from both trees in a primary and secondary forest were assessed for N-cycle metrics and DNA sequence-based comp...

We examined the activation and effector functions of lung macrophages in mediating immunity against helminth parasites. Using fate mapping mice, we showed that monocytes recruited to the lung assume an alveolar macrophage phenotype and comprise as many as 10% of alveolar macrophages by 7 days after inoculation. Monocyte-derived alveolar macrophages...

Type 2 cytokine responses promote parasitic immunity and initiate tissue repair; however, they can also result in immunopathologies when not properly restricted. Although basophilia is recognized as a common feature of type 2 inflammation, the roles basophils play in regulating these responses are unknown. Here, we demonstrate that helminth-induced...

Anti-helminth responses require robust type 2 cytokine production that simultaneously promotes worm expulsion and initiates the resolution of helminth-induced wounds and hemorrhaging. However, how infection-induced changes in hematopoiesis contribute to these seemingly distinct processes remains unknown. Recent studies have suggested the existence...

Tuberculosis, caused by Mycobacterium tuberculosis, kills 1.6 million people annually. To bridge the gap between structure- and cell-based drug discovery strategies, we are pioneering a computer-aided discovery paradigm that merges structure-based virtual screening with ligand-based, machine learning methods trained with cell-based data. This appro...

Non-small cell lung cancer (NSCLC) is a complex disease in need of new methods of therapeutic intervention. Recent interest has focused on using microRNAs (miRNAs) as a novel treatment method for various cancers. miRNAs negatively regulate gene expression post-transcriptionally, and have become attractive candidates for cancer treatment because the...

This study shows that Vochysia guatemalensis tree plantations were associated with enhanced soil biotic and abiotic characteristics in previously cleared forests in the Northern Zone of Costa Rica, suggesting the possible use of this practice as a restoration strategy for local land owners. Soil samples from a primary forest (PF), secondary forest...

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The use of predatory bacteria as a potential live therapeutic to control human infection is gaining increased attention. Earlier work with Micavibrio spp. and Bdellovibrio spp. has demonstrated the ability of these predators to control drug-resistant Gram-negative pathogens, Tier-1 select agents and biofilms. Additional studies also confirmed that...

Waters Award Recipient ABRF 2017 Awarded for Outstanding Scientific Poster at the Association of Biomolecular Resource Facilities (ABRF) 2017 annual meeting and given an Oral Presentation. Orlando, R. (2017). Outstanding Scientific Poster Awards for the ABRF 2017 Organized by the Education Committee and Sponsored by Waters Corporation. Journal of...