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Dr Terri Meehan-Andrews Senior Lecturer, Rural Human Biosciences

Terri is part of the regional Human Bioscience that services all of the courses offered in LaTrobe Rural Health School. She teaches into several first and second year Allied Health Physiology and Pathophysiology subjects, and into 3rd year Pharmacology in FSTE. Her expertise is within reproduction and pregnancy, but also has extensive knowledge of endocrinology and the immune system. She coordinates several subjects, including DEN2MDA (Dentistry Pathophysiology), HBS2PAT (instance subject) and part of ORH1OHB (Infection and Immunity)

Terri's current research strengths can be divided into 2 areas:

1/ Lab based research Current cancer therapies such as radiotherapy and chemotherapy, while effective, have considerable drawbacks in the form of off-target damage to normal tissues and toxicity to organs such as the heart. Both forms of therapy also suffer from resistance and relapse. A common pathway by which both act is through damage to the tumour DNA. By understanding the ways in which tumours repair their DNA and in which they resist cell death we can find targets for small molecules which should sensitize the tumour cells to the effects of radiation and cytotoxic drugs such as doxorubicin. This would enable the use of much lower doses of radiation and cytotoxic drugs with more effective killing, less resistance and fewer effects on normal tissues and organs.

Exploring the time dependent changes on the sensitivity of breast cancer cells to various chemotherapies (tamoxifen) in a hypoxic environment.

Cancer is a very heterogeneous disease, in which cells at various stages of neoplasia exist within one tumour mass. Within this tumour mass are cells with varying degrees of oxygen and nutrient supply with cells in the centre of the mass being more deficient. It has been shown that tumour stem cells are to found amongst these hypoxic populations and that these cells are particularly resistant to treatment via both radiation and chemotherapy. Following treatment these resistant stem cells form the basis of relapse or reoccurrence. These surviving cells undergo further transformation and, following relapse, are usually a more aggressive type. Traditional methods for studying the effect on chemotherapy in vitro utilise incubators under normoxic conditions (normal oxygen levels). By utilising a hypoxic chamber, we can manipulate the oxygen supply and assess the different response of cells to various treatment options in both normoxic and hypoxic conditions.

Exploring the apoptotic potential of ABT-737, as a means to sensitize breast cancer cells to certain chemotherapies (doxorubicin).

Many cancers possess the ability to override the normal apoptotic mechanisms that would normally lead to cell death. This leads to resistance to therapeutic modalities such as radiation and chemotherapy. The balance between members of the bcl-2 family, including both pro-apoptotic and anti-apoptotic, determines the fate of many cells. In cancer, the normal ratios of these members has been disrupted to favour survival, in breast cancer several studies have shown bcl-2, bcl-w, bcl-xl and mcl-1 to be up regulated to varying degrees, and highest levels have been linked to poorer prognosis. In recent years, to sensitise cancer cells to apoptotic inducing therapies, several compounds have been developed to reduce the anti-apoptotic effect of Bcl-2 family members and thus allow stimulation of apoptosis in cancer cells. One such compound, ABT-737, is proving to have beneficial effects in multiple myeloma, and other blood borne cancers, but its effectiveness on breast cancer, which also displays a substantial increase in bcl-2 family members, has been limited. ABT-737, was designed to displace BH3 only proteins from bcl-xl (and also bcl-2 and bcl-w) thus allowing the mitochondrial outer membrane permeabilization to occur, and thus apoptosis. In breast cancers, we are exploring combining BH3-mimetics (e.g. ABT-737) with doxorubicin in an attempt to enhance apoptosis. In particular we wish to unravel the time-dependent molecular changes in response to this combination in order more exactly to understand the mechanism of action and possible reasons for failure of this combination therapy.

Anthracyclines, targeted therapies and GnRHR, triple therapies for triple negative breast cancer.

Triple-negative breast cancer (TNBC) is defined by tumours lacking estrogen and progesterone receptors as well as lacking the epidermal growth factor receptor 2 (EGFR2).While receptor positive breast cancers have proven to be amenable to a variety of receptor targeted therapies such as Tamoxifen and Herceptin, chemotherapy is the only systemic therapy for TNBC.There are no specific treatment guidelines for TNBC although the tumours are considered to be chemosensitive and the anthracyclines doxorubicin and epirubicin figure prominently in treatment regimes. Treatment for TNBC is relatively ineffective when compared to receptor positive tumours and the combination of chemotherapy with agents targeting pathways such as apoptosis and DNA repair has not lead to significant improvements. A greater understanding of the apoptotic and DNA repair pathways in TNBC treated with anthracyclines is necessary. Another potential target which has been little investigated in TNBC is the gonadotropin releasing hormone receptor, GnRHR . This is known to be expressed on at least half TNBC cases and may be a promising target in combination with anthracyclines and small molecule targeted therapies.

2/ Scholarship of Teaching - Terri is very passionate about her teaching and strives to develop, implement and then assess succesful programs. She currenlty has several lines of investigation into student learning and subject effectiveness. Terri explores if current teaching methods nurture and promote a self learning approach. This project has two stages, firstly, to ascertain the changing learning styles (Visual, Aural, Reading, and Kinesthetic) of students in 1st, 2nd and 3rd year of a health science degree. Secondly, to develop teaching practices that evolve throughout the three years that develop the skills to learn independently and be adaptive to different learning approaches. Ultimately her aim is to support students to gain confidence in their ability to 'self learn' and develop into life-long learners.

Positions

selected publications