A5018506614- Trypanosoma species research and implications
- Renal Diseases and Glomerulopathies
- Lysosomal Storage Disorders Research
- Complement system in diseases
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Research on Leishmaniasis Studies
- Immune Cell Function and Interaction
- Evolution and Genetic Dynamics
- Electrochemical sensors and biosensors
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- Calcium signaling and nucleotide metabolism
- HIV Research and Treatment
- Lipoproteins and Cardiovascular Health
- Pancreatitis Pathology and Treatment
City University of New York
2019-2021
Hunter College
2020-2021
New York University
2008-2016
Albert Einstein College of Medicine
2015
NYU Langone Health
2009
Significance African trypanosomes are parasites that can cause sleeping sickness in humans. Humans and some primates, but not other mammals, have a gene called APOL1 protects against certain trypanosomes. Genetic variants arose Africa strongly associated with kidney disease Americans. These disease-associated may risen to high frequency because they defend humans particularly pathogenic trypanosome. In this paper, we show how has evolved by analyzing the distribution of these then...
Significance African trypanosomes are parasites that can cause sleeping sickness in humans. Host defense against some of these is provided by the human serum factor apolipoprotein L-1 (APOL1), which causes swelling and lysis susceptible trypanosomes. Lysis follows uptake APOL1 into acidic parasite endosomes thought to involve ion influx across plasma membrane. In this paper we show that, after interaction with lipid bilayers at pH, subsequent pH neutralization triggers opening pH-gated...
Recently evolved alleles of Apolipoprotein L-1 ( APOL1 ) provide increased protection against African trypanosome parasites while also significantly increasing the risk developing kidney disease in humans. protects infections by forming ion channels within parasite, causing lysis. While correlation to is robust, there little consensus concerning underlying mechanism. We show human cells that renal variants have a population active at plasma membrane, which results an influx both Na + and Ca...
The human innate immunity factor apolipoprotein L-I (APOL1) protects against infection by several protozoan parasites, including Trypanosoma brucei Endocytosis and acidification of high-density lipoprotein-associated APOL1 in trypanosome endosomes leads to eventual lysis the parasite due increased plasma membrane cation permeability, followed colloid-osmotic swelling. It was previously shown that recombinant inserts into planar lipid bilayers at acidic pH form pH-gated nonselective channels...
Several species of African trypanosomes cause fatal disease in livestock, but most cannot infect humans due to innate trypanosome lytic factors (TLFs). Human TLFs are pore forming high-density lipoprotein (HDL) particles that contain apolipoprotein L-I (apoL-I) the trypanolytic component, and haptoglobin-related protein (Hpr), which binds free hemoglobin (Hb) blood facilitates uptake TLF via a haptoglobin-hemoglobin receptor. The human-infective Trypanosoma brucei rhodesiense escapes lysis...
Human immunodeficiency virus type 1 (HIV-1)-infected T cells form a virological synapse with noninfected CD4(+) in order to efficiently transfer HIV-1 virions from cell cell. The is specialized cellular junction that similar some respects the immunological involved T-cell activation and effector functions mediated by antigen receptor. stops migration allow sustained interaction between T-cells antigen-presenting cells. Here, we have asked whether envelope gp120 presented on surface mimic an...
Humans are protected against infection from most African trypanosomes by lipoprotein complexes present in serum that contain the trypanolytic pore-forming protein, Apolipoprotein L1 (APOL1). The human-infective trypanosomes, Trypanosoma brucei rhodesiense East Africa and T. b. gambiense West have separately evolved mechanisms allow them to resist APOL1-mediated lysis cause human trypanosomiasis, or sleeping sickness, man. Recently, APOL1 variants were identified a subset of Old World...
Apolipoprotein L-I (APOL1) is a channel-forming effector of innate immunity. The common human APOL1 variant G0 provides protection against infection with certain Trypanosoma and Leishmania parasite species, but it cannot protect the trypanosomes responsible for African trypanosomiasis. Human variants G1 G2 human-infective also confer higher risk developing chronic kidney disease. Trypanosome-killing activity dependent on ability to insert into membranes at acidic pH form pH-gated cation...
The human apolipoprotein L gene family encodes the L1–6 (APOL1–6) proteins, which are effectors of innate immune response to viruses, bacteria and protozoan parasites. Due a high degree similarity between APOL it is often assumed that they have similar functions APOL1, forms cation channels in planar lipid bilayers membranes resulting cytolytic activity. However, channel properties remaining proteins not been reported. Here, we used transient overexpression bilayer system study function...
Trypanosomiasis is a devastating neglected tropical disease that affects millions of livestock and thousands humans each year. Only two subspecies Trypanosoma brucei can cause in humans, while immunity to most trypanosomes mediated primates by HDL-associated circulating complexes called trypanosome lytic factors (TLFs) 1 2. Both TLFs are similar composition, though TLF2 uniquely contains non-covalently associated IgM antibodies, the role origin which remain unclear. Here, we show these...