Bench and Beyond; Tales from... Dr Tanjina Kader, CCV Postdoctoral Fellow, Gorringe Lab (Precision Cancer Medicine Lab), Women’s Cancer Research Program

I always wanted to do something significant for patients while growing up in Bangladesh, preferably as a clinician scientist. I was too young to understand the complexity of the congenital orphan disease I had, however, I did understand that there are many hard working, extremely motivated clinicians who helped me with my frequent chest pain, blood transfusion, fever, infections and so on. I was misdiagnosed at first with thalassemia, a non-curable blood disorder when I was four. Eventually after a year or so, a magical person (scientist) who specialised in blood disorders, found out that this particular haemolytic anaemia is curable by splenectomy and I would no longer require blood transfusion after removing my spleen. Most importantly, it was not thalassemia, therefore, I will survive! I grew up being in hospitals more than in schools; every second week with various diagnostic tests (with a grumpy face), let alone those frequent nasty chest pains I had to endure till I was 12! I did develop a huge interest on Science since primary school, in fact, I had my own small lab where I was collecting Tamarind seeds with which I definitely was planning some kind of experiments (what was I thinking?!!). That under-funded lab existed only about a year though.

After completing year 12 in Bangladesh, I came to Australia to do my undergraduate degree on Biomedical Science, simply because I was fascinated about human biology. During my 2nd year of undergraduate at La Trobe University I was amazed by my Biochemistry lectures along with Epigenetics, Medicinal Chemistry, and Immunology. The latter comes naturally since curing my disease with splenectomy came with the huge consequence of a much suppressed immune system (frequent tonsillitis, ear infection and antibiotics became part of my life). My biomedical science degree allowed me to know about various diseases including cancer. I still remember those days where we were given “case studies” to discuss, right after every disease section was completed, and I was thrilled to see scientists investigating even the rarest of diseases.

I followed my passion for proteins and drugs and went on to do an Honours thesis on the effectiveness of a drug on lipoproteins and reactive oxygen species using multiple transgenic mice models of cardiovascular disease at the University of Otago, NZ. I transitioned to working as a Research Assistant in the same lab, investigating a very rare lethal condition affecting the protein HDL, called Tangier disease. As I was working using patient samples of a very rare condition, this was very rewarding at a personal level.

I had long wanted to do a PhD, but at the same time, I still felt I could not concentrate on one single protein for the rest of my life. Thankfully, I went to Prof. Peter Campbell’s talk when he visited Otago, where he showed the power of precision medicine in childhood leukaemia. That was it: I knew I had to follow that path since that will take me as close as possible to patients. Unfortunately, I soon realised precision medicine is largely based on Cancer Genomics, Cancer Evolution and Bioinformatics. None of these I had ever studied. My undergraduate mentors from La Trobe advised to apply for a PhD at Peter Mac and both Prof Ian Campbell and A/Prof Kylie Gorringe gave me the incredible opportunity to come and join their lab as a PhD student.

My recently completed PhD project was understanding precancerous breast lesions at their molecular level using archival patient specimens. The goal being to see how we can use this genetic knowledge for estimating risk for cancer. There are substantial biopsies diagnosed with these lesions with uncertain malignant potential (known as B3 lesions) globally (300,000-400,000 cases in the USA alone/year) after routine mammogram. We made a significant shift in understanding breast cancer origin and progression from one of the high risk lesions, atypical ductal hyperplasia (ADH) such that ADH has a multipotent nature and can progress to any grade or intrinsic subtype of breast cancer, including high grade, ER- and ERBB2 amplified cancer. Our data changed the paradigm for ADH, which was previously only thought to progress to low grade cancer. A subset of breast papillary lesions, another type of B3 lesion, can progress to any grade of ductal breast cancer, if left untreated. This was another novel finding since papillary lesions were only thought to progress to breast cancer with papillary histology.

A large number of women diagnosed with B3 lesions are routinely being over treated, primarily to confirm there is no cancer in nearby tissue and secondarily to prevent the lesion becoming cancer in the future. Without surgery, it is not possible by imaging alone to determine if there is co-existing cancer associated with B3 lesions. For more than two decades, attempts have been made to identify the subset of women with a B3 lesion who could safely be observed rather than being treated with surgical excision and/or chemoprevention. However, no reliable biomarkers or molecular tests are available to accurately stratify women by their risk.

I therefore proposed a combined immuno-molecular biomarker (combination of total lymphocytes count and chromosomal changes) and envisioned a clinical model for optimal therapy selection. Currently, my work as a Post doc involves developing a clinically feasible assay using this approach and validating this combined biomarker in a large national and international combined patient cohort. I am also incredibly interested in exploring how tumour cells and immune cells co-evolve and how the immune environment correlates with the genetic makeup of the tumour. Specifically, how do some cells with the low-level chromosomal aberrations (i.e. not diploid), but not all, in the premalignant setting bypass the initial immune recognition (i.e. innate immunity) and eventually progress to an aggressive tumour? Currently, I am thinking of utilising a new technology to image multiple immune cells simultaneously which will allow me to tease the innate immune system out of these lesions, especially investigating my most favourite one: Natural Killer (NK) cells and their ligands. This eventually can lead to an in depth understanding of the correlation of the level of aneuploidy and immune recognition and how breast tumour progress from these premalignant lesions.

While being fascinated about ADH, I am also highly passionate to understand the recurrence of ductal carcinoma in situ (DCIS)/pre-invasive using single cell technologies. DCIS can often recur as an invasive cancer and understanding the biology how they achieve this remains unclear to date. This understanding will help the Gorringe Lab to propose a highly desirable prognostic biomarker for DCIS recurrence. Again, this will help patients to stratify who are at their highest risk of recurrences based on their genetic profile (i.e. personally tailored prognosis). 

Working at the Peter Mac and Gorringe Lab in particular, has enabled me to enhance my interest and passion toward precision medicine. Even though I am in a cancer genetics lab, I have expanded my knowledge, interest and work on the immune-genomic landscape. More importantly, I feel very privileged to walk in this building every morning and work with many highly motivated, talented and compassionate clinicians and scientists. Whether I work on patients’ cases, attend multidisciplinary meeting or visit the clinic, I absolutely love my work since it allows me to live my dream every day and work with patients as close as possible. I dream of being useful for patients every day, translating my discoveries into clinic. I love to believe that as scientists, all of us have incredible power to utilise our knowledge on patients’ welfare and we should use it very passionately yet carefully.

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Figure caption: Gains (more than 2 copies) of an oncogene (ZNF217) (white arrows) in breast tumour by using Fluorescence in situ hybridisation (FISH)

Dr Tanjina Kader is a Postdoctoral Researcher in Women’s Cancer Research Program under the supervision of A/P Kylie Gorringe. She obtained her PhD in 2019 on Cancer Genetics at the Sir Peter MacCallum Cancer Centre, Department of Oncology, University of Melbourne. Recently, she has been awarded the postdoctoral fellowship for a year from Cancer Council Victoria to continue her work towards a combined immune molecular biomarker for breast cancer risk prediction to reduce overtreatment after a mammogram. 

Contact:

Email: [email protected]
Twitter: @TanjinaKader
Linked In: https://www.linkedin.com/in/tanjina-kader-1a99aab4/