Dr Allison Pettit

Ph.D.

Senior Research Fellow

About me

I am a Senior Research Fellow leading the Bone and Immunology Research Group at Mater Research-UQ. My current research activity examines the complex and diverse interactions between bone and immune cells. I undertook my PhD (APA scholarship, PhD conferred in August 2000) at The University of Queensland Centre for Immunology and Cancer Research characterizing the role of dendritic cells (DC) in the pathogenesis of rheumatoid arthritis (RA), providing a strong foundation in immunology.

I subsequently undertook my first postdoctoral positions (Research Fellow and subsequently Instructor in Medicine) at Beth Israel Deaconess Medical Centre, Harvard Medical School (supported at various stages by an Australian Rheumatology Association (ARA) Heald Fellowship, NHMRC CJ Martin Fellowship or Arthritis Foundation (USA) Fellowship).

During this time I gained high quality training in bone biology. Since returning to Australia I have continue to successfully undertake and fund independent research activities, firstly within the CRC for Chronic Inflammatory Diseases at the Institute for Molecular Bioscience and subsequently at UQ-CCR. During this time I’ve been supported by NHMRC, CJ Martin Fellowship and subsequently Career Development Award, NHMRC project grants and smaller philanthropic grants. Over my career I’ve received numerous awards for my research contributions including an ARA Young Investigator Award and the John H Tyrer Prize in Internal Medicine (UQ).

With a little over 11 years postdoctoral experience I have 45 original scientific publications including 15 first or co-first author and 3 senior author contributions with 2 of my first author contributions ranking in the top 1% of publications for their field and a H index of 20 (source: Essential Science Indicators, ISI Web of Knowledge). I have successfully supervised numerous postgraduate students including 2 conferred PhDs who were both awarded Dean’s commendations for their theses and won numerous awards throughout their candidatures.

Projects

Bones and Immunology

Musculoskeletal diseases and injury are a leading cause of chronic disability and are a substantial and increasing burden on health systems and individuals worldwide. Prevention and treatment of many bone diseases is currently inadequate. Macrophages have been indirectly implicated in many bone diseases, linking aberrant macrophage function to bone damage. However it was our recent discovery of specialized macrophages within bone tissues (osteomacs) that highlighted macrophages have a prominent and direct role in bone physiology and disease. Osteomacs are associated with sites of bone formation, bone resorption and bone remodelling and can directly control the function of the specialized cells that build and remove bone. Our ongoing research is investigating the molecular mediators involved in this communication and the impact of positively or negatively targeting macrophages on reaching and maintaining peak bone health.

 

We are also investigating the contribution of macrophages to bone repair after injury/fracture. Fracture repair can be broken down into 3 basic phases: inflammatory (clean up the injury and gather repair components), anabolic (form a temporary boney structure bridging the injury) and catabolic (remodel the temporary structure to re-instate normal bone architecture and mechanics). Our results show that macrophages are essential for establishing bone repair during the early inflammatory phase of bone healing. A sustained presence of macrophages is also required for optimal bone repair during the anabolic phase. Our research is examining whether macrophages can be targeted to accelerate fracture repair. Also under investigation is whether aberrant macrophage biology is an underlying cause of the compromised bone healing commonly associated with co-morbidities such as osteoporosis, diabetes, obesity and chronic inflammatory disease.

 

Our third research focus is the contribution of resident bone marrow (BM) macrophages, including osteomacs, to hematopoietic stem cell (HSC) biology. This is in collaboration with the Stem Cell Biology and Cancer and Stem Cell Groups within the Mater Research Blood and Bone Program. The region in BM that is closest to bone surfaces (endosteum) has been shown to be the preferred site of residence of true HSC and contains specialized environments called endosteal stem cell niches. We have shown that osteomacs/macrophages are an integral component of these niches. Our specific interest is to determine if osteomacs/macrophages are required for successful bone marrow/HSC transplantation and whether enhancing osteomacs/macrophages is a viable strategy for improving transplantation outcomes.

 

Major Projects:

  1. Targeting macrophages as a therapeutic strategy for accelerating or correcting healthy and compromised fracture healing.
  2. The role of macrophages in facilitating haematopoietic stem cell engraftment and reconstitution.
  3. Elucidation of the molecular mediators responsible for osteomac regulation of osteoblast and osteoclast function.
  4. Phenotypic and functional characterization of resident macrophages populations in periosteum, endosteum and central bone marrow.
Targeting macrophages to improve fracture repair; Do recipient macrophages persist and support stem cell engratment following bone marrow transplantation; Macrophage regulation of bone biology.

Research fields

Osteoimmunology, macrophage biology, bone biology and stem cell niches