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Overview

Sarah Diermeier image
Dr Sarah Diermeier.

We are dedicated to developing innovative molecular medicines and diagnostics for hard to treat indications. Our diverse team of scientists spans all aspects of drug development from target identification and validation to payload design, formulation and delivery, and drug testing using the latest translational research models.

We develop a wide range of modalities including RNA medicines, CRISPR/Cas based approaches and small molecules. Our technology is positioned to address indications in human and animal health such as cancer, neurodegenerative, cardiovascular and infectious diseases and rare genetic disorders.
Our team comprises experts in computational biology, molecular biology, biochemistry, genetics, chemistry, pharmacology, medicine and pharmaceutical sciences.

Contact

Dr Sarah Diermeier
Email sarah.diermeier@otago.ac.nz

Research

Therapeutic Nanomedicine

Therapeutic nanomedicine is the medical application of nanotechnology, encompassing technologies that can diagnose, treat or prevent disease. We mainly focus on the development of novel therapeutics and drug delivery systems.

Our theme researchers on the Dunedin, Wellington and Christchurch Campuses are investigating innovative nanomedicines from gene therapy to RNA therapeutics and small molecules fighting various diseases. Research is funded by HRC, Marsden and MBIE in collaboration with national and international collaborators. Many of our researchers are engaged in translational and applied projects and aim to commercialize their research through the filing and licensing of patents or spinning out new companies.

Ongoing research in the Therapeutic Nanomedicine theme includes:

Targeting antibiotic resistant bacteria

We are in era where bacteria have developed resistance to multiple antibiotics and pose one of the greatest threats to human health. The Pletzer has developed a murine skin infection model that forms the basis for the development and investigation of novel therapeutics to address the global problem of antimicrobial resistance to improve health and treatment. We are interested in compounds that exhibit broad-spectrum activity towards bacterial biofilms and/or work by neutralizing bacterial infection rather than just killing them. The lab also works on strategies to overcome bacterial resistance mechanisms by developing antibiotic-conjugates and nano-formulations that increase the uptake efficiency of already approved drugs. We offer collaborative work to test new nanomedicines in the fight against hard-to-treat WHO-priority pathogens.

RNA therapeutics for hard-to-treat cancers

The Diermeier Lab is developing new generation RNA therapeutics for oncology, focusing on cancer types that have extremely poor outcomes such as triple-negative breast cancer, metastatic colorectal cancer and glioblastoma. Our world-leading target identification pipeline combines computational biology and CRISPR screening approaches to find the best clinically actionable RNA molecules. We are experts in a relatively unexplored area of RNA biology, the field of long non-coding RNA , also referred to as “dark matter” of the genome. Currently, we design and develop antisense oligonucleotides ( ASO s) to drug these “dark matter” genes with high specificity, aiming to inhibit cancer growth and spread. We test our novel medicines in innovative translational model systems such as patient-derived tumoroids that can act as personalized patient avatars. The lab recently spun out the venture-backed startup Amaroq Therapeutics, which is pioneering formal preclinical and clinical development of lnc RNA -targeting drugs.

Personalized medicines for ultra-rare diseases

A collaborative project lead by Prof Hughes aims to develop personalized drugs for rare and ultra-rare (including n=1) diseases such as Batten disease. New avenues of nanomedicine are explored to find the best treatment strategy for each individual patient, including gene therapy, enzyme replacement therapy, drug repurposing and RNA therapeutics. International collaborations with leading academics and biotech companies ensure access to cutting-edge therapies, providing hope for New Zealanders with otherwise limited treatment options.

Diagnostic Nanomedicine

Diagnostic nanomedicine aims to identify disease-causing biomolecules (such as proteins or nucleic acids) and develop new methods of detecting them.

Ongoing research in the Diagnostic Nanomedicine theme includes:

Improving genetic health through RNA diagnostics

The development of next-generation sequencing technologies over the past decade has revolutionized genetic testing of high-risk cancer patients in a diagnostic setting. New sequencing technologies offer increasingly affordable and more powerful approaches for obtaining detailed genetic information. In genomic medicine, this information is used to direct clinical care of patients and their whānau and has significant implications for disease prevention and treatment. While genomic technologies offer great potential to transform clinical care, interpreting the test results is a major challenge for health care professionals. The Walker and Lau labs aim to address this challenge by developing methods for applying evidence from laboratory assays to determine the clinical significance of DNA sequence variants. Results from this study will have both national and international significance through our various roles in international expert panels that are tasked with improving diagnostic guidelines for clinical and research labs around the world.

Our people

Our team comprises experts in computational biology, molecular biology, biochemistry, genetics, chemistry, pharmacology, medicine and pharmaceutical sciences.

Nanomedicine research leader

Dr Sarah Diermeier, RNA medicines, non-coding RNA , antisense oligonucleotides ( ASO s)

Investigators

External collaborators

  • Dr Emma Nolan, University of Auckland
  • Professor Gavin Painter, Victoria University of Wellington / Malaghan
  • Associate Professor Alex Gavryushkin, University of Canterbury
  • Associate Professor Rakesh Veedu, Murdoch University / Syngenis

Students

  • Holly Pinkney, PhD student
  • Joke Grans, PhD student
  • Kaitlyn Tippett, PhD student
  • Amy Bennie, PhD student
  • Kiri-Moana Burich, MSc student

Publications

Chang, K.-C., Diermeier, S. D., Yu, A. T., Brine, L. D., Russo, S., Bhatia, S., … Spector, D. L. (2020). MaTAR25 LncRNA regulates the Tensin1 gene to impact breast cancer progression. bioRxiv. doi: 10.1101/2020.02.03.931881

Rana, Z., Diermeier, S., Hanif, M., & Rosengren, R. J. (2020). Understanding failure and improving treatment using HDAC inhibitors for prostate cancer. Biomedicines, 8(2), 22.  doi: 10.3390/biomedicines8020022

Arun, G., Diermeier, S. D., & Spector, D. L. (2018). Therapeutic targeting of long non-coding RNAs in cancer. Trends in Molecular Medicine, 24(3), 257-277.  doi: 10.1016/j.molmed.2018.01.001

Diermeier, S. D., Chang, K.-C., Freier, S. M., Song, J., El Demerdash, O., Krasnitz, A., … Spector, D. L. (2016). Mammary tumor-associated RNAs impact tumor cell proliferation, invasion, and migration. Cell Reports, 17(1), 261-274.  doi: 10.1016/j.celrep.2016.08.081

Arun, G., Diermeier, S., Akerman, M., Chang, K.-C., Wilkinson, J. E., Hearn, S., … Spector, D. L. (2016). Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes & Development, 30(1), 34-51. doi: 10.1101/gad.270959.115

Diermeier, S., Kolovos, P., Heizinger, L., Schwartz, U., Georgomanolis, T., Zirkel, A., … Papantonis, A. (2014). TNFα signalling primes chromatin for NF-κB binding and induces rapid and widespread nucleosome repositioning. Genome Biology, 15(12), 536.  doi: 10.1186/s13059-014-0536-6

Diermeier, S. D., Németh, A., Rehli, M., Grummt, I., & Längst, G. (2013). Chromatin-specific regulation of mammalian rDNA transcription by clustered TTF-I binding sites. PLoS Genetics, 9(9), e1003786.  doi: 10.1371/journal.pgen.1003786

Schubert, T., Pusch, M. C., Diermeier, S., Benes, V., Kremmer, E., Imhof, A., & Längst, G. (2012). Df31 protein and snoRNAs maintain accessible higher-order structures of chromatin. Molecular Cell, 48(3), 434-444.  doi: 10.1016/j.molcel.2012.08.021

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