My thesis dissertation titled “Identification and characterization of somatic mutations associated with progression of Acute Myeloid Leukemia having FLT3ITD and screening of small-molecule inhibitors in treatment of AMLFLT3ITD” at Cancer Science Institute (CSI) of Singapore, National University of Singapore (NUS) was the ideal experience to acquire skills in molecular cloning, cell culture, protein biochemistry, bioinformatics and exome sequencing.
The molecular pathogenesis of Acute Myeloid Leukemia has not been completely deciphered yet but develops through a multistep acquisition of a wide range of somatic mutations. Therefore, investigation of cancer genome sequences and structures provide insights for understanding cancer biology,
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During this period, I was involved in two other projects on biology of Lamc2 in tumor progression of Anaplastic thyroid cancer and Pancreatic Cancer. The Thyroid Cancer study titled “Laminin-5 gamma-2 (LAMC2) is highly expressed in anaplastic thyroid carcinoma and is associated with tumor progression, migration and invasion by modulating signaling of EGFR” was published in the Journal for Clinical Endocrinology and Metabolism (JCEM) recently. I am studying the same mechanisms and pathway in Pancreatic cancer now. The pancreatic cancer project is also showing promising results and the paper is in preparation for publication.
After graduating in Genetic Engineering in August 2013, I was keen on exploring the field of developmental biology. I’m now an intern in the developmental epigenetics and diseases unit at Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore supervised by Dr Daniel M Messerschmidt on genomic imprinting during development of an organism. In this study, I’m studying the role of TRIM28 and its effects of knockdown in Embryonic Stem Cells. Dr Daniel Messerschmidt just started as a junior PI and I am the only member in his lab. Apart from experiments, I also manage laboratory supplies and utilities. This has given me an opportunity to work independently with minimal guidance.
Short-term projects and supplementary training during summer and winter of 2010,2011 and 2012 in Tumor induction (Induction of Hepatocellular carcinoma
These cancer cells lose control of the growth and it begins to spread around the body, or in this case, in blood forming tissues such as bone marrow, spleen, and lymph nodes. Therefore, homeostasis is not maintained as the growth of cancerous cells is uncontrollable. In the diagram, the gene ABL1 goes through a small mutation which causes the disastrous disease of cancer. Mutations allow rapid growth, cannot stop uncontrolled cell growth, and make errors when repairing DNA mistakes. Specifically, in this case, there is a change in the amino acid protein which is why Tyr changes into IIe. In the first picture below, we can see that in a normal DNA strand, the nitrogenous base adenine and thymine go together and cytosine and guanine match
Cancer is the name given to a collection of more than 100 related diseases. It is a genetic disease caused by changes to genes that control the way our cells function (“What is Cancer?” National Cancer Institute). The genetic changes that subsidize cancer tend to affect three chief types of genes- proto-oncogenes, tumor suppressor genes, and DNA repair genes. These are the “drivers” of cancer. Cancer can appear and grow virtually anywhere in the body. Types of cancer are customarily named for the organs or tissues where they form. They can also be described by the types of cell that formed them. Although there are many different kinds of cancer, all cancers start because abnormal cells grow out of control (“What is Cancer?” American Cancer
Tumour cells contain many mutated and misregulated genes, some of which the tumour requires for its survival, growth or metastasis. Overexpressed proteins have previously made good drug targets, for example Trastuzumab targets Her2 in breast cancer and Gleevec targets BCR-ABL in CML. When studying a potential novel drug target, I would search the literature and online databases such as Oncomine to determine whether the gene is known to be misregulated or mutated in human cancers. I would be particularly interested in studies on the effects of tumourigenesis when the potential target has been overexpressed or knocked-down/out,
Though initial treatment of acute lymphoblastic leukemia (ALL) leads to clinical and hematological remission, 20% of pediatric ALL patients and over 50% of adult ALL patients relapse and cannot achieve remission even after intensified therapy, making disease relapse and resistance to therapy the greatest challenge. This study aims to determine the cellular and genetic mechanisms, specifically with NT5C2, responsible for drug resistance and relapse in ALL. It was hypothesized that relapse-associated NT5C2 mutations may represent gain-of-function alleles with increased enzymatic activity.
The mutation abnormally activates AKT1 kinase, allowing cells to grow and divide without control . This abnormal cell proliferation leads to the development of cancerous tumors. Although the Glu17Lys mutation has been reported in only a few types of cancer, increased activity (expression) of the AKT1 gene is found in many types of cancer (Lindhurst et al., 2011; Carpten
Over the years, evidence has proven that any mutations on chromosomes whether they are broken, missing or repositioned is not just a side effect of cancer, but can be an increasing factor for
Cancer is beyond mutations. By definition, epigenetics is the change in gene translation that is caused by alterations not directly due to genetic mutations in the DNA sequence. The 2 main mechanisms are DNA methylation and covalent modification of histones. By methylation, certain molecular tags (methyl groups) bind to a specific sequence of a gene, that results in its disability hence incapable of being translated into its appropriate protein product. These changes affect the cell’s functions leaving its DNA unchanged. Epi is derived from Latin meaning above; hence an epigenetic configuration overlies our genetic predispositions.
Globally, cancer is one of the leading causes of death (Fitzmaurice et al., 2015; WHO, 2012). It is continue to consider as a pandemic disease, take into account it's increasingly prevalence rate worldwide (Jacox, Daniel & Payne, 1994; American Cancer Society, 2015).
Scientists from George Washington University medical center have found a missing link in mitosis that brings hope for cancer researchers. They have found a protein known as Arpc 1b that is an activator for an enzyme called Aurora A that is important in early stages of cellular reproduction. Cells divide and separate poles to create new cells. If all goes well two new cells are produced, but in some cases the protein is over used, and abnormal cells are produced which lead to cancer. Pharmaceutical industries are targeting Aurora A and trying to prevent it. This is the next step to help scientists find a way to stop the activity of Arpc in cancer cells. As an example, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. They are among the worlds leading biotech companies, with multiple products on the market and a promising development pipeline. At Genentech, James Sabry, M.D., Ph.D. who is the Vice President, said, “If we understand basic science, our drugs make it to market. If we don’t, the company dies.” Roche, Genentech’s parent company, spends more on research and development than any country in the world ($9.5 billion annually). Understanding cell development and cell division help the
Acute lymphoblastic leukemia(ALL), also known as lymphoblastic leukemia/lymphoma in the WHO classification, is a malignant expansion of immature lymphoid cells that results from multi-step genetic changes in a single lymphoid progenitor cell. Its incidence peaks between the ages of 2 and 4 years(1(.
There are many different types and variations of leukemia, and not all types have singular, concrete causes associated with them. One of the four most common types of leukemia, acute myeloid leukemia, is characterised by the unregulated growth of blasts which
Importantly, the ERM protein ezrin itself is a well-known mediator of metastasis (Elliott et al., 2005; Khanna et al., 2004; Meng et al., 2010). Many clinical studies have linked high expression of ezrin with poor outcome in cancer patients suffering from a wide variety of cancers, including prostate, breast can lung cancer (Clucas and Valderrama, 2014). Interestingly, specifically the abnormal distribution of ezrin in breast cancer patients, from the apical regions of non-tumorigenic cells to motile projections in invasive cells, has been correlated with poor prognosis (Sarrio et al., 2006). In addition, it has previously been indicated as an important regulator of metastasis in the murine carcinoma cell line AC2M2 (Elliott et al., 2005). Furthermore, ezrin overexpression has been shown in various studies to promote the survival, migration and/or invasion of cancer cells into surrounding tissue and to disrupt cell-cell contacts (Clucas and Valderrama, 2014).
Interest in cancer has grown recently as it has been one of the most fatal causes of death yet; there has only recently been an advance in the understanding the cellular basis of cancer. Due to today’s understanding of cancer it has been acknowledges that the disease disregards the rules of normal cell division, as a group of abnormal cells grow uncontrollably. Cancer is described as being the unnecessary development of cells within the body. Individual’s genetic tendency contains a significant role in the cancerous growths, as the genetic information of an individual can’t be controlled. In order to understand the cellular basis of cancerous cells and there difference between normal cells, there are certain aspects in which need to be addressed that being; DNA replication and translation, oncogenes and protogenes, tumor suppression genes, how tumour cells work, apoptosis and cell death, blood vessel growth (angiogenesis) and metastasis.
Cancer is a tragedy that has affected families around the world for thousands of years. This disease has been a mystery, until recent discoveries have begun to unravel its origins, treatments, and causes. Cancer is important to understand because it’s vast impact on the world today. There are ways to lower the chances of getting cancer as well as removing it. Anyone is capable of getting cancer but the three main factors that can cause it is genetic traits, life choices, and environmental surroundings.
The luminal A subtype of breast cancer had the highest frequency of PIK3CA mutation (45%), and the basal subtype had the lowest (9%). Additional identified aberrations resulting in the dysregulation of the PI3K/mTOR pathway include Akt and PTEN mutations, or loss of PTEN protein [11,12].