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Papers by Mannu Walia

Research paper thumbnail of PTHrP, its receptor, and protein kinase A activation in osteosarcoma

Molecular & Cellular Oncology, 2014

In osteosarcoma, knockdown of the parathyroid hormone-related protein (PTHrP) receptor reduces ac... more In osteosarcoma, knockdown of the parathyroid hormone-related protein (PTHrP) receptor reduces activation through cyclic AMP-dependent protein kinase A (PKA) and substantially decreases tumor differentiation, invasion, and proliferation in vivo. These findings complement other evidence supporting a central role of the PKA pathway in osteosarcoma biology and pathogenesis.

Research paper thumbnail of Murine models of osteosarcoma: a piece of the translational puzzle

Journal of cellular biochemistry, Jan 13, 2017

Osteosarcoma (OS) is the most common cancer of bone in children and young adults. Despite extensi... more Osteosarcoma (OS) is the most common cancer of bone in children and young adults. Despite extensive research efforts, there has been no significant improvement in patient outcome for many years. An improved understanding of the biology of this cancer and how genes frequently mutated contribute to OS may help improve outcomes for patients. Whilst our knowledge of the mutational burden of OS is approaching saturation, our understanding of how these mutations contribute to OS initiation and maintenance is less clear. Murine models of OS have now been demonstrated to be highly valid recapitulations of human OS. These models were originally based on the frequent disruption of p53 and Rb in familial OS syndromes, which are also common mutations in sporadic OS. They have been applied to significantly improve our understanding about the functions of recurrently mutated genes in disease. The murine models can be used as a platform for preclinical testing and identifying new therapeutic targe...

Research paper thumbnail of Efficacy of Ibrutinib, Rituximab and Mini-CHOP in Very Elderly Patients with Newly Diagnosed Diffuse Large B Cell Lymphoma: Primary Analysis of the Australasian Leukaemia & Lymphoma Group NHL29 Study

Blood, 2021

Introduction R-mini-CHOP is an established standard of care in elderly patients with DLBCL, with ... more Introduction R-mini-CHOP is an established standard of care in elderly patients with DLBCL, with a 2yr OS of 59% and PFS of 47% (Peyrade et al, Lancet Oncol 2011). The addition of ibrutinib to full dose R-CHOP in younger pts with DLBCL has efficacy, but significant toxicity limits the ability to complete therapy in pts ≥60 yrs (Younes et al, JCO 2019). We previously demonstrated the deliverability of ibrutinib with R-mini-CHOP in 80 pts ≥75yrs with DLBCL with a median average relative total dose of 97%; 77% of pts received 6 cycles of R-mini-CHOP despite SAEs in 62% (Verner et al, Haematol Oncol 2019). Here we present the primary efficacy endpoint and key secondary and exploratory endpoints. Methods This was a prospective, multicenter, single-arm, phase 2 study of patients aged ≥75yrs with newly diagnosed DLBCL. Pts received six 21-day cycles of ibrutinib 560mg/d and R-mini-CHOP (Rituximab 375mg/m 2, cyclophosphamide 400mg/m 2, doxorubicin 25mg/m 2, vincristine 1mg on day 1 & predni...

Research paper thumbnail of Single-tube linear DNA amplification (LinDA) for robust ChIP-seq

Nature Methods, 2011

Genome-wide profiling of transcription factors based on massive parallel sequencing of immunoprec... more Genome-wide profiling of transcription factors based on massive parallel sequencing of immunoprecipitated chromatin (ChIP-seq) requires nanogram amounts of DNA. Here we describe a high-fidelity, single-tube linear DNA amplification method (LinDA) for ChIP-seq and reChIP-seq with picogram DNA amounts obtained from a few thousand cells. This amplification technology will facilitate global analyses of transcription-factor binding and chromatin with very small cell

Research paper thumbnail of PTHrP, its receptor, and protein kinase A activation in osteosarcoma

Molecular & Cellular Oncology, 2014

In osteosarcoma, knockdown of the parathyroid hormone-related protein (PTHrP) receptor reduces ac... more In osteosarcoma, knockdown of the parathyroid hormone-related protein (PTHrP) receptor reduces activation through cyclic AMP-dependent protein kinase A (PKA) and substantially decreases tumor differentiation, invasion, and proliferation in vivo. These findings complement other evidence supporting a central role of the PKA pathway in osteosarcoma biology and pathogenesis.

Research paper thumbnail of Murine models of osteosarcoma: a piece of the translational puzzle

Journal of cellular biochemistry, Jan 13, 2017

Osteosarcoma (OS) is the most common cancer of bone in children and young adults. Despite extensi... more Osteosarcoma (OS) is the most common cancer of bone in children and young adults. Despite extensive research efforts, there has been no significant improvement in patient outcome for many years. An improved understanding of the biology of this cancer and how genes frequently mutated contribute to OS may help improve outcomes for patients. Whilst our knowledge of the mutational burden of OS is approaching saturation, our understanding of how these mutations contribute to OS initiation and maintenance is less clear. Murine models of OS have now been demonstrated to be highly valid recapitulations of human OS. These models were originally based on the frequent disruption of p53 and Rb in familial OS syndromes, which are also common mutations in sporadic OS. They have been applied to significantly improve our understanding about the functions of recurrently mutated genes in disease. The murine models can be used as a platform for preclinical testing and identifying new therapeutic targe...

Research paper thumbnail of Efficacy of Ibrutinib, Rituximab and Mini-CHOP in Very Elderly Patients with Newly Diagnosed Diffuse Large B Cell Lymphoma: Primary Analysis of the Australasian Leukaemia & Lymphoma Group NHL29 Study

Blood, 2021

Introduction R-mini-CHOP is an established standard of care in elderly patients with DLBCL, with ... more Introduction R-mini-CHOP is an established standard of care in elderly patients with DLBCL, with a 2yr OS of 59% and PFS of 47% (Peyrade et al, Lancet Oncol 2011). The addition of ibrutinib to full dose R-CHOP in younger pts with DLBCL has efficacy, but significant toxicity limits the ability to complete therapy in pts ≥60 yrs (Younes et al, JCO 2019). We previously demonstrated the deliverability of ibrutinib with R-mini-CHOP in 80 pts ≥75yrs with DLBCL with a median average relative total dose of 97%; 77% of pts received 6 cycles of R-mini-CHOP despite SAEs in 62% (Verner et al, Haematol Oncol 2019). Here we present the primary efficacy endpoint and key secondary and exploratory endpoints. Methods This was a prospective, multicenter, single-arm, phase 2 study of patients aged ≥75yrs with newly diagnosed DLBCL. Pts received six 21-day cycles of ibrutinib 560mg/d and R-mini-CHOP (Rituximab 375mg/m 2, cyclophosphamide 400mg/m 2, doxorubicin 25mg/m 2, vincristine 1mg on day 1 & predni...

Research paper thumbnail of Single-tube linear DNA amplification (LinDA) for robust ChIP-seq

Nature Methods, 2011

Genome-wide profiling of transcription factors based on massive parallel sequencing of immunoprec... more Genome-wide profiling of transcription factors based on massive parallel sequencing of immunoprecipitated chromatin (ChIP-seq) requires nanogram amounts of DNA. Here we describe a high-fidelity, single-tube linear DNA amplification method (LinDA) for ChIP-seq and reChIP-seq with picogram DNA amounts obtained from a few thousand cells. This amplification technology will facilitate global analyses of transcription-factor binding and chromatin with very small cell

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