Georgette D. Kanmogne

Last updated

Georgette D. Kanmogne
Born
Cameroon
NationalityAmerican
Alma mater University of Yaoundé
University of Bristol
University of Cambridge
Known forMechanisms of blood brain barrier HIV infiltration
Awards2012 Distinguished Scientist Award - University of Nebraska Medical Center, 2006 Nicolas Badami Fellowship Award for Excellence in HIV/AIDS Research, 2005 American Lung Association Career Investigator Award
Scientific career
FieldsVirology, genetics, neuroimmunology
Institutions University of Nebraska Medical Center

Georgette D. Kanmogne is a Cameroonian American geneticist and molecular virologist and a full professor and vice chair for resource allocation and faculty development within the Department of Pharmacology and Experimental Neurosciences at the University of Nebraska Medical Center in Omaha, Nebraska. Kanmogne's research program focuses on exploring the pathogenesis of neuroAIDS by deciphering the mechanisms underlying blood brain barrier dysfunction and viral entry into the central nervous system. Her research also addresses the lack of HIV therapies that cross the blood brain barrier (BBB) and has played a critical role in the development of nanoparticles encapsulating HIV-drugs that can cross the BBB to prevent viral-mediated neuron death in the brain. Kanmogne collaborates with clinical and basic researchers across America, Cameroon, and West Africa, spanning disciplines from hematology to psychiatry, to explore how viral genetic diversity is correlated with the neurological impact of HIV.

Contents

Early life and education

Kanmogne was born and raised in Cameroon. [1] She was one of six children in her family and was the first of all of them to attend high school or college. [2] In her adolescent years, Kanmogne was an altar server and sang in the youth choir at her parish. [2] She contemplated becoming a nun throughout high school, though by the time she graduated, she had recognized her passion for science and had committed to pursuing an undergraduate degree at the University of Yaoundé in Cameroon. [2]

Kanmogne completed her Bachelor of Science in Zoology in 1987, and then pursued her Master's of Science in biochemistry at the University of Yaoundé, completing her degree in 1989. [3] For two years following her Master's, from 1990 to 1992, Kanmogne worked as a Laboratory Instructor in the Department of Biochemistry at the University of Yaoundé. [3]

In 1992, Kanmogne moved to the United Kingdom to pursue her graduate training at the University of Bristol. [3] She studied Molecular Parasitology under the mentorship of Wendy C. Gibson, exploring the biology of Trypanosoma brucei . [4] Kanmogne used a novel genetic technique at the time, random amplification of polymorphic DNA (RAPD), to characterize the genetic heterogeneity of T. brucei gambiense isolates from endemic areas in Africa. [5] Her work was the first to show that the RAPD method is as accurate as the RFLP method at characterizing genetic variation, while also achieving a more detailed genetic analysis. [5] Kanmogne also explored more effective ways to diagnose sleeping sickness caused by T. brucei since its levels are very low. [6] She developed a novel PCR method that was highly sensitive and could be used to effectively diagnose sleeping sickness at levels of 25 trypanosomes/ml of blood. [6]

Kanmogne completed her graduate training in 1996, and stayed in the United Kingdom for her postdoctoral work at the University of Cambridge in the Department of Haematology. [7] She began studying HIV during her postdoc, specifically exploring the CD4+ T-lymphocyte levels in patients with AIDS as well as the specific biology of human T-cell leukaemia virus type I infection in West African patients with AIDS. [8]

In 1998, Kanmogne moved to the United States to pursue further postdoctoral training in the Department of Pathology at the University of Oklahoma Health Sciences Center. [3] While continuing to study HIV, Kanmogne pursued a Master of Public Health in Biostatistics and Epidemiology at the University of Oklahoma Health Sciences Center from 2000 to 2002. [3]

Under the mentorship of Ronald C. Kennedy, Kanmogne continued to study HIV, but now with an emphasis on the infiltration of HIV into the central nervous system and the lungs. [9] Since the exact mechanisms of HIV invasion into the brain as well as subsequent neuronal cell death were unknown, Kanmogne's work explored the susceptibility of brain endothelial cells and cortical neurons to HIV-1 infection. [9] She discovered that neither cell type expressed the known HIV receptors, CXCR4 and CCR5, and thus other cell types or mechanisms just mediate CNS-HIV infection. [9] Kanmogne then explored using non-human primate (NHP) microglia to study HIV pathogenesis in the brain. [10] She found that NHP microglia express HIV-1 receptors and can be used to study HIV pathogenesis. [10]

In addition to studying HIV infection in the CNS, Kanmogne also explored HIV infection in the lung since the onset of AIDS is associated with severe pulmonary complications. [11] She found that human lung microvascular endothelial cells are not a major reservoir of HIV in the lungs, but they do represent a target for the lethal effects of HIV viral proteins. [11]

Career and research

In 2002, Kanmogne was hired as a research assistant professor in the Department of Pathology at the University of Oklahoma Health Science Center. She continued to study the vascular biology of HIV infection and the effects of HIV infection on the central nervous system. [7]

Kanmogne was then recruited to the University of Nebraska Medical Center in 2005 where she became an assistant professor in the Department of Pharmacology and Experimental Neuroscience, as well as a senior scientist in the Center for Neurovirology and Neurodegenerative Disorders. [7] In 2008, she was promoted to associate professor and became the vice chair for resource allocation and faculty development within the Department of Pharmacology and Experimental Neuroscience. [12] In 2012, Kanmogne received tenure and in 2015, she was promoted to full professor within the department. [12] Kanmogne is a member of the American Society for Virology and the International Society for NeuroVirology. [13]

At the University of Nebraska Medical Center, Kanmogne is also the principal investigator of a lab that explores the mechanisms of HIV-1 brain invasion and the vascular biology of HIV infection. [14] Her work has led to critical discoveries about the role of blood brain barrier (BBB) interactions with HIV as well as how these interactions influence the immune response in the brain leading to neuroAIDS, including neurodegeneration and AIDS associated dementia. [14] She has found that HIV affects the biology of the brain endothelium and that proximity of HIV-infected peripheral macrophages to the brain can lead to increased immune signalling, BBB facilitated infiltration of peripheral leukocytes into the brain. [14] Kanmogne is also deeply committed to extensive collaboration and diversity in academia. [1] She currently collaborates with several departments within the University of Yaoundé in Cameroon and the University of California San Diego, and her international research project explores the viral genetic diversity of HIV infections in Cameroon and West Africa. [13] She hopes that her projects will enhance the ability of healthcare workers in Cameroon and West Africa to better diagnose and treat HIV. [15] Further, since Cameroon has some of the highest diversity of HIV strains and subtypes, her work exploring the genetic variants of HIV in relation to neurological symptoms will help to highlight potential disease trajectories associated with each subtype as well as open up possibilities for novel therapeutic development. [15]

HIV infected monocytes and blood brain barrier dysfunction

Kanmogne and her colleagues discovered that the HIV-1 envelope glycoprotein, gp120, activates the CCR5 and CXCR4 receptors on the surface of human brain microvasculature endothelial cells (HBMECs) leading to toxicity and BBB leakage. [16] They further showed that blocking gp120 or its associated receptors actually prevents monocyte migration and permeability of the BBB via the PKC pathway. [16] Kanmogne and her colleagues later found that HIV-1 causes STAT-1 activation in HBMECs leading to IL-6 expression which mediates the recruitment of monocytes across the BBB. [17] To further delineate the mechanisms of HIV-infection leading to neuroinflammation, Kanmogne and her colleagues found that the CCR5 chemokine receptor mediated HIV-1 binding to HBMECs and that cross talk between STAT1 and PI3K pathways were mediating the BBB dysfunction after HIV infection. [18]

Cognitive impairments due to HIV

Kanmogne and her colleagues also hoped to explore the cognitive impairments due to HIV infection in Sub-Saharan Africa, so developed novel methods to do so. [19] The team reported the first normative data for executive function and verbal fluency in Cameroonians and this established the ability to use this method for future assessments of cognitive function in patients with and without HIV infection. [19] They further conducted a cross-sectional study of the HIV-associated neurocognitive disorders (HAND) using the International HIV Dementia Scale among a population in Cameroon. [20] They found that the risk factors for HAND are similar to those described in other studies, underscoring the need to start to assess risk factors as a means of HANDS prevention in Cameroon. [20]

Nanomedicines for HIV

In order to treat the neurocognitive symptoms of HIV, therapeutics must enter the brain so Kanmogne and her team are developing novel nanomedicines to achieve this. [21] The first developed a nanoformulated crystalline antiretroviral therapy in 2012 which allows for drugs to be passed through the BBB through cell-to-cell contact between monocytes and HBMECs. [22] They found that the therapy in mice led to decreased activation of glial cells and decreased viral load in the spleen. [22] Next, they developed a method in 2018 that uses polyanhydride nanoparticles containing antioxidants that are internalized and then transferred from monocytes to HBMECs in order to protect neurons from oxidative stress associated with infection and inflammation. [21] This therapy showed positive results in its potential to be used as a method to enhance drug transport across the BBB. [21]

Awards and honors

Related Research Articles

<span class="mw-page-title-main">HIV</span> Human retrovirus, cause of AIDS

The human immunodeficiency viruses (HIV) are two species of Lentivirus that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.

<span class="mw-page-title-main">CCR5</span> Immune system protein

C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.

<span class="mw-page-title-main">Envelope glycoprotein GP120</span> Glycoprotein exposed on the surface of the HIV virus

Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1988. The 120 in its name comes from its molecular weight of 120 kDa. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. These receptors are DC-SIGN, Heparan Sulfate Proteoglycan and a specific interaction with the CD4 receptor, particularly on helper T-cells. Binding to CD4 induces the start of a cascade of conformational changes in gp120 and gp41 that lead to the fusion of the viral membrane with the host cell membrane. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds.

A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell.

HIV-associated neurocognitive disorders (HAND) are neurological disorders associated with HIV infection and AIDS. It is a syndrome of progressive deterioration of memory, cognition, behavior, and motor function in HIV-infected individuals during the late stages of the disease, when immunodeficiency is severe. HAND may include neurological disorders of various severity. HIV-associated neurocognitive disorders are associated with a metabolic encephalopathy induced by HIV infection and fueled by immune activation of macrophages and microglia. These cells are actively infected with HIV and secrete neurotoxins of both host and viral origin. The essential features of HIV-associated dementia (HAD) are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Cognitive impairment is characterised by mental slowness, trouble with memory and poor concentration. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include apathy, lethargy and diminished emotional responses and spontaneity. Histopathologically, it is identified by the infiltration of monocytes and macrophages into the central nervous system (CNS), gliosis, pallor of myelin sheaths, abnormalities of dendritic processes and neuronal loss.

<span class="mw-page-title-main">CCL5</span> Mammalian protein found in Homo sapiens

Chemokine ligand 5 is a protein which in humans is encoded by the CCL5 gene. The gene has been discovered in 1990 by in situ hybridisation and it is localised on 17q11.2-q12 chromosome. It is also known as RANTES. RANTES was first described by Dr. Tom Schall who named the protein, the original source of the name Rantes was from the Argentine movie Man Facing Southeast about an alien who shows up in a mental ward who was named Rantés, the rather clunky acronym was only made to fit the name.

Chemokine ligands 4 previously known as macrophage inflammatory protein (MIP-1β), is a protein which in humans is encoded by the CCL4 gene. CCL4 belongs to a cluster of genes located on 17q11-q21 of the chromosomal region. Identification and localization of the gene on the chromosome 17 was in 1990 although the discovery of MIP-1 was initiated in 1988 with the purification of a protein doublet corresponding to inflammatory activity from supernatant of endotoxin-stimulated murine macrophages. At that time, it was also named as "macrophage inflammatory protein-1" (MIP-1) due to its inflammatory properties.

Chemokine ligand 1 (CCL1) is also known as small inducible cytokine A1 and I-309 in humans. CCL1 is a small glycoprotein that belongs to the CC chemokine family.

<span class="mw-page-title-main">CCL7</span> Mammalian protein found in Homo sapiens

Chemokine ligand 7 (CCL7) is a small cytokine that was previously called monocyte-chemotactic protein 3 (MCP3). CCL7 is a small protein that belongs to the CC chemokine family and is most closely related to CCL2.

Host tropism is the infection specificity of certain pathogens to particular hosts and host tissues. This explains why most pathogens are only capable of infecting a limited range of host organisms.

<span class="mw-page-title-main">Maraviroc</span> Antiretroviral drug

Maraviroc, sold under the brand names Selzentry (US) and Celsentri (EU), is an antiretroviral medication used to treat HIV infection. It is taken by mouth. It is in the CCR5 receptor antagonist class.

Visna-maedi virus from the genus Lentivirus and subfamily Orthoretrovirinae, is a retrovirus that causes encephalitis and chronic pneumonitis in sheep. It is known as visna when found in the brain, and maedi when infecting the lungs. Lifelong, persistent infections in sheep occur in the lungs, lymph nodes, spleen, joints, central nervous system, and mammary glands; The condition is sometimes known as ovine progressive pneumonia (OPP), particularly in the United States, or Montana sheep disease. White blood cells of the monocyte/macrophage lineage are the main target of the virus.

<span class="mw-page-title-main">CCR2</span> Mammalian protein found in Homo sapiens

C-C chemokine receptor type 2 (CCR2 or CD192 is a protein that in humans is encoded by the CCR2 gene. CCR2 is a CC chemokine receptor.

Peptide T is an HIV entry inhibitor discovered in 1986 by Candace Pert and Michael Ruff, a US neuroscientist and immunologist. Peptide T, and its modified analog Dala1-peptide T-amide (DAPTA), a drug in clinical trials, is a short peptide derived from the HIV envelope protein gp120 which blocks binding and infection of viral strains which use the CCR5 receptor to infect cells.

Gero Hütter is a German hematologist. Hütter and his medical team transplanted bone marrow deficient in a key HIV receptor to a leukemia patient, Timothy Ray Brown, who was also infected with human immunodeficiency virus (HIV). Subsequently, the patient's circulating HIV dropped to undetectable levels. The case was widely reported in the media, and Hütter was named one of the "Berliners of the year" for 2008 by the Berliner Morgenpost, a Berlin newspaper.

CCR5 receptor antagonists are a class of small molecules that antagonize the CCR5 receptor. The C-C motif chemokine receptor CCR5 is involved in the process by which HIV, the virus that causes AIDS, enters cells. Hence antagonists of this receptor are entry inhibitors and have potential therapeutic applications in the treatment of HIV infections.

The Berlin patient is an anonymous person from Berlin, Germany, who was described in 1998 as exhibiting prolonged "post-treatment control" of HIV viral load after HIV treatments were interrupted.

<span class="mw-page-title-main">HIV/AIDS research</span> Field of immunology research

HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

A small proportion of humans show partial or apparently complete innate resistance to HIV, the virus that causes AIDS. The main mechanism is a mutation of the gene encoding CCR5, which acts as a co-receptor for HIV. It is estimated that the proportion of people with some form of resistance to HIV is under 10%.

<span class="mw-page-title-main">Robyn S. Klein</span> American neuroimmunologist

Robyn S. Klein is an American neuroimmunologist as well as the Vice Provost and Associate Dean for Graduate Education at Washington University in St. Louis Missouri. Klein is also a professor in the Departments of Medicine, Anatomy & Neurobiology, and Pathology & Immunology. Her research explores the pathogenesis of neuroinflammation in the central nervous system by probing how immune signalling molecules regulate blood brain barrier permeability. Klein is also a fervent advocate for gender equity in STEM, publishing mechanisms to improve gender equity in speakers at conferences, participating nationally on gender equity discussion panels, and through service as the president of the Academic Women’s Network at the Washington University School of Medicine.

References

  1. 1 2 Georgette Kanmogne, Ph.D., MPH. , retrieved June 5, 2020
  2. 1 2 3 "Meet UNMC Distinguished Scientist Georgette Kanmogne, Ph.D., M.P.H." unmc.edu. April 23, 2012. Retrieved June 5, 2020.
  3. 1 2 3 4 5 6 7 8 "Georgette Kanmogne, Ph.D., M.P.H., Biographical Information". unmc.edu. Retrieved June 5, 2020.
  4. ↑ "Georgette D Kanmogne's research works | University of Nebraska Medical Center, Nebraska (UNMC) and other places". ResearchGate. Retrieved June 5, 2020.
  5. 1 2 Kanmogne, G; Stevens, Jamie; Asonganyi, Tazoacha; Gibson, W (February 1, 1996). "Genetic heterogeneity in the Trypanosama brucei gambiense genome analysed by random amplification of polymorphic DNA". Parasitology Research. 82 (6): 535–41. doi:10.1007/s004360050158. PMID   8832735. S2CID   20988925.
  6. 1 2 Kanmogne, G; Asonganyi, Tazoacha; Gibson, W (November 1, 1996). "Detection of Trypanosoma brucei gambiense, in serologically positive but aparasitaemic sleeping-sickness suspects in Cameroon, by PCR". Annals of Tropical Medicine and Parasitology. 90 (5): 475–83. doi:10.1080/00034983.1996.11813072. PMID   8915123.
  7. 1 2 3 4 5 "Georgette D. Kanmogne, Ph.D. MPH | Nebraska Center for Virology | Nebraska". www.unl.edu. Retrieved June 5, 2020.
  8. ↑ Kanmogné, G; Sangaré, A; d'Almeida, O; Adu-Sarkodie, Yaw; Davies, F; Lee, H; Allain, J (December 1, 1998). "Human T-cell leukaemia/lymphoma virus type I infection in West African patients with clinical AIDS". AIDS. 12 (16): 2239. PMID   9833874.
  9. 1 2 3 Kanmogne, G; Grammas, Paula; Kennedy, R (January 1, 2001). "Analysis of human endothelial cells and cortical neurons for susceptibility to HIV-1 infection and co-receptor expression". Journal of Neurovirology. 6 (6): 519–28. doi:10.3109/13550280009091952. PMID   11175324.
  10. 1 2 Kanmogne, Georgette; Kennedy, Ronald; Grammas, Paula (June 1, 2002). "Infection of Baboon Microglia with SIV–HIV Recombinant Viruses: Role of CD4 and Chemokine Receptors". AIDS Research and Human Retroviruses. 18 (8): 557–65. doi:10.1089/088922202753747905. PMID   12036485.
  11. 1 2 Kanmogne, Georgette; Kennedy, Ronald; Grammas, Paula (February 1, 2001). "Analysis of Human Lung Endothelial Cells for Susceptibility to HIV Type 1 Infection, Coreceptor Expression, and Cytotoxicity of gp120 Protein". AIDS Research and Human Retroviruses. 17 (1): 45–53. doi:10.1089/088922201750056771. PMID   11177382.
  12. 1 2 "Georgette Kanmogne, Ph.D., M.P.H." unmc.edu. Retrieved June 5, 2020.
  13. 1 2 3 "Biosketches of Speakers: 10th Anniversary BRAIN Disorders Symposium 2014" (PDF). NIH.gov. 2014. Retrieved June 5, 2020.
  14. 1 2 3 4 "International Society for NeuroVirology" (PDF). isnv.org. May 2009. Retrieved June 5, 2020.
  15. 1 2 "Dr. Kanmogne aims to improve AIDS care in Cameroon". unmc.org. March 13, 2012. Retrieved June 4, 2020.
  16. 1 2 Kanmogne, Gd; Schall, K; Leibhart, J; Knipe, B; Gendelman, He; Persidsky, Y (January 2007). "HIV-1 gp120 Compromises Blood-Brain Barrier Integrity and Enhances Monocyte Migration Across Blood-Brain Barrier: Implication for Viral Neuropathogenesis". Journal of Cerebral Blood Flow and Metabolism. 27 (1): 123–34. doi:10.1038/sj.jcbfm.9600330. PMC   2232899 . PMID   16685256.
  17. ↑ Chaudhuri, Anathbandhu; Yang, Bo; Gendelman, Howard E.; Persidsky, Yuri; Kanmogne, Georgette D. (February 15, 2008). "STAT1 signaling modulates HIV-1–induced inflammatory responses and leukocyte transmigration across the blood-brain barrier". Blood. 111 (4): 2062–2072. doi:10.1182/blood-2007-05-091207. ISSN   0006-4971. PMC   2234049 . PMID   18003888.
  18. ↑ B, Yang; S, Singh; R, Bressani; Gd, Kanmogne (November 1, 2010). "Cross-talk Between STAT1 and PI3K/AKT Signaling in HIV-1-induced Blood-Brain Barrier Dysfunction: Role of CCR5 and Implications for Viral Neuropathogenesis". Journal of Neuroscience Research. 88 (14): 3090–101. doi:10.1002/jnr.22458. PMC   4300945 . PMID   20568281.
  19. 1 2 Kanmogne, Georgette D.; Fonsah, Julius Y.; Tang, Bin; Doh, Roland F.; Kengne, Anne M.; Umlauf, Anya; Tagny, Claude T.; Nchindap, Emilienne; Kenmogne, Léopoldine; Franklin, Donald; Njamnshi, Dora M. (December 12, 2018). "Effects of HIV on executive function and verbal fluency in Cameroon". Scientific Reports. 8 (1): 17794. Bibcode:2018NatSR...817794K. doi: 10.1038/s41598-018-36193-7 . ISSN   2045-2322. PMC   6290794 . PMID   30542105.
  20. 1 2 Ak, Njamnshi; Ac, Bissek; P, Ongolo-Zogo; En, Tabah; Az, Lekoubou; Fn, Yepnjio; Jy, Fonsah; Ct, Kuate; Sa, Angwafor (October 15, 2009). "Risk Factors for HIV-associated Neurocognitive Disorders (HAND) in sub-Saharan Africa: The Case of Yaoundé-Cameroon". Journal of the Neurological Sciences. 285 (1–2): 149–53. doi:10.1016/j.jns.2009.06.043. PMC   4906943 . PMID   19631349.
  21. 1 2 3 Tm, Brenza; Bw, Schlichtmann; B, Bhargavan; Je, Vela Ramirez; Rd, Nelson; Mg, Panthani; Jm, McMillan; B, Kalyanaraman; He, Gendelman (November 2018). "Biodegradable Polyanhydride-Based Nanomedicines for Blood to Brain Drug Delivery". Journal of Biomedical Materials Research. Part A. 106 (11): 2881–2890. doi:10.1002/jbm.a.36477. PMC   6366942 . PMID   30369055.
  22. 1 2 Gd, Kanmogne; S, Singh; U, Roy; X, Liu; J, McMillan; S, Gorantla; S, Balkundi; N, Smith; Y, Alnouti (2012). "Mononuclear Phagocyte Intercellular Crosstalk Facilitates Transmission of Cell-Targeted Nanoformulated Antiretroviral Drugs to Human Brain Endothelial Cells". International Journal of Nanomedicine. 7: 2373–88. doi: 10.2147/IJN.S29454 . PMC   3357981 . PMID   22661891.
  23. ↑ "Sixth Scientist Laureate, distinguished scientists named". unmc.org. February 20, 2012. Retrieved June 4, 2020.
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