Ajit Johnson

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Ajit Johnson
Ajit Johnson Nirmal.jpg
Dr. Nirmal at the Intelligent Systems for Molecular Biology conference in 2015
Born
Chennai, India
Alma mater
Known for
Scientific career
Institutions Harvard University, Dana–Farber Cancer Institute
Website www.ajitjohnson.com

Ajit Johnson Nirmal is a cancer geneticist. He has also campaigned to raise awareness on tech addiction and net neutrality. [1] [2]

Contents

Education

Born in Vellore, Johnson graduated with a bachelor's degree in biotechnology at Karunya University. Johnson graduated from University College London in 2011 and worked at the Indian Institute of Science. He earned a Doctor of Philosophy in cancer genetics and genomics from the University of Edinburgh [3] and performed his post-doctoral work at Harvard Medical School and Dana Farber Cancer Institute. [4]

Career

Research

Johnson and colleagues developed a cell based gene therapy for haemophilia patients at the National Cancer Centre Singapore. [5] [6] Johnson developed ImSig, a network-based computational framework that facilitates the characterization of immune cells within the tumor microenvironment. [7] Johnson's work involves multi-dimensional characterization (genetic, transcriptional, spatial and biophysical attributes) of the tumor ecosystem [8] and understanding the differences in molecular signature of immune cells [9] across tumours.

Related Research Articles

Antigen Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. The term antigen originally referred to a substance that is an antibody generator. Antigens can be proteins, peptides, polysaccharides, lipids, or nucleic acids.

Metastasis Spread of a disease inside a body

Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues.

The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostasis.

Chimeric antigen receptor T cells are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy.

Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral immunotherapy. These branches use three different types of treatment methods: gene overexpression, gene knockout, and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout uses RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths. In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.

Indoleamine 2,3-dioxygenase Mammalian protein found in Homo sapiens

Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO EC 1.13.11.52) is a heme-containing enzyme physiologically expressed in a number of tissues and cells, such as the small intestine, lungs, female genital tract or placenta. In humans is encoded by the IDO1 gene. IDO is involved in tryptophan metabolism. It is one of three enzymes that catalyze the first and rate-limiting step in the kynurenine pathway, the O2-dependent oxidation of L-tryptophan to N-formylkynurenine, the others being indolamine-2,3-dioxygenase 2 (IDO2) and tryptophan 2,3-dioxygenase (TDO). IDO is an important part of the immune system and plays a part in natural defense against various pathogens. It is produced by the cells in response to inflammation and has an immunosuppressive function because of its ability to limit T-cell function and engage mechanisms of immune tolerance. Emerging evidence suggests that IDO becomes activated during tumor development, helping malignant cells escape eradication by the immune system. Expression of IDO has been described in a number of types of cancer, such as acute myeloid leukemia, ovarian cancer or colorectal cancer. IDO is part of the malignant transformation process and plays a key role in suppressing the anti-tumor immune response in the body, so inhibiting it could increase the effect of chemotherapy as well as other immunotherapeutic protocols.

Understanding of the antitumor immunity role of CD4+ T cells has grown substantially since the late 1990s. CD4+ T cells (mature T-helper cells) play an important role in modulating immune responses to pathogens and tumor cells, and are important in orchestrating overall immune responses.

The Cancer Genome Atlas (TCGA) is a project to catalogue the genetic mutations responsible for cancer using genome sequencing and bioinformatics. The overarching goals was to apply high-throughput genome analysis techniques to improve the ability to diagnose, treat, and prevent cancer through a better understanding of the genetic basis of the disease.

PD-L1 Mammalian protein found in Homo sapiens

Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the CD274 gene.

Tumor-infiltrating lymphocytes

Tumor-infiltrating lymphocytes are white blood cells that have left the bloodstream and migrated towards a tumor. They include T cells and B cells and are part of the larger category of ‘tumor-infiltrating immune cells’ which consist of both mononuclear and polymorphonuclear immune cells, in variable proportions. Their abundance varies with tumor type and stage and in some cases relates to disease prognosis

Cellular senescence Phenomenon characterized by the cessation of cell division

Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process is known as "replicative senescence", or the Hayflick limit. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things.

Molecular oncology is an interdisciplinary medical specialty at the interface of medicinal chemistry and oncology that refers to the investigation of the chemistry of cancer and tumors at the molecular scale. Also the development and application of molecularly targeted therapies.

Tumor microenvironment

The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.

Patient derived xenografts (PDX) are models of cancer where the tissue or cells from a patient's tumor are implanted into an immunodeficient or humanized mouse. PDX models are used to create an environment that allows for the natural growth of cancer, its monitoring, and corresponding treatment evaluations for the original patient.

Immune checkpoint Regulators of the immune system

Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulating immune checkpoint targets.

The Immunologic Constant of Rejection (ICR), is a notion introduced by biologists to group a shared set of genes expressed in tissue destructive-pathogenic conditions like cancer and infection, along a diverse set of physiological circumstances of tissue damage or organ failure, including autoimmune disease or allograft rejection. The identification of shared mechanisms and phenotypes by distinct immune pathologies, marked as a hallmarks or biomarkers, aids in the identification of novel treatment options, without necessarily assessing patients phenomenologies individually.

The dendritic cell-based cancer vaccine is an innovation in therapeutic strategy for cancer patients.

A cancer-associated fibroblast (CAF) is a cell type within the tumor microenvironment that promotes tumorigenic features by initiating the remodelling of the extracellular matrix or by secreting cytokines. CAFs are a complex and abundant cell type within the tumour microenvironment; the number cannot decrease, as they are unable to undergo apoptosis.

Li Zhang is a biologist currently working at University of Texas at Dallas. She is a professor of Biological Sciences and the Cecil H. and Ida Green Distinguished Chair in Systems Biology Science at University of Texas at Dallas. During her 20+ years of independent research, Li Zhang has made major contributions to understanding of heme signaling and function in gene regulation, neuronal differentiation and survival, and lung cancer bioenergetics.

Edward F. Fritsch is a scientist in the field of molecular biology and cancer immunology.

References

  1. Cashin, Declan. "These Posters Perfectly Sum Up Twentysomethings' Addiction to the Internet". BuzzFeed.
  2. Bulkley, McKenna. "The Truth About #ThisGeneration". www.huffingtonpost.com.
  3. Nirmal, Ajit Johnson (28 September 2018). "British Library Thesis Collection". University of Edinburgh.{{cite web}}: CS1 maint: url-status (link)
  4. Nirmal, Ajit Johnson. "Harvard Scholar- Ajit Johnson Nirmal".
  5. Sivalingam, Jaichandran; Kenanov, Dimitar; Han, Hao; Nirmal, Ajit Johnson; Ng, Wai Har; Lee, Sze Sing; Masilamani, Jeyakumar; Phan, Toan Thang; Maurer-Stroh, Sebastian; Kon, Oi Lian (1 March 2016). "Multidimensional Genome-wide Analyses Show Accurate FVIII Integration by ZFN in Primary Human Cells". Molecular Therapy. 24 (3): 607–619. doi:10.1038/mt.2015.223. ISSN   1525-0016. PMC   4786920 . PMID   26689265.
  6. Lee, Sze Sing; Sivalingam, Jaichandran; Nirmal, Ajit J.; Ng, Wai Har; Kee, Irene; Song, In Chin; Kiong, Chin Yong; Gales, Kristoffer A.; Chua, Frederic; Pena, Edgar M.; Ogden, Bryan E. (1 July 2018). "Durable engraftment of genetically modified FVIII‐secreting autologous bone marrow stromal cells in the intramedullary microenvironment". Journal of Cellular and Molecular Medicine. 22 (7): 3698–3702. doi:10.1111/jcmm.13648. ISSN   1582-1838. PMC   6010829 . PMID   29682884.
  7. Nirmal, Ajit J.; Regan, Tim; Shih, Barbara B.; Hume, David A.; Sims, Andrew H.; Freeman, Tom C. (28 September 2018). "Immune Cell Gene Signatures for Profiling the Microenvironment of Solid Tumors". Cancer Immunology Research. 6 (11): 1388–1400. doi: 10.1158/2326-6066.CIR-18-0342 . ISSN   2326-6066. PMID   30266715.
  8. Nirmal, Ajit Johnson. "Harvard Scholar Page". Harvard University.{{cite web}}: CS1 maint: url-status (link)
  9. Shih, Barbara B; Nirmal, Ajit J; Headon, Denis J; Akbar, Arne N; Mabbott, Neil A; Freeman, Tom C (1 April 2017). "Derivation of marker gene signatures from human skin and their use in the interpretation of the transcriptional changes associated with dermatological disorders". The Journal of Pathology. 241 (5): 600–613. doi:10.1002/path.4864. ISSN   0022-3417. PMC   5363360 . PMID   28008606.