Publications

Link to Khokha Lab Pubmed

Link to Khokha Lab Google Scholar Citations

 

Recent Publications (in the last three years)

2023

Hourglass, a rapid analysis framework for heterogeneous bioimaging data, identifies sex disparity in IL-6/STAT3-associated immune phenotypes in pancreatic cancer

Aliar K, Waterhouse HR, Vyas F, Krebs N, Zhang B, Poulton E, Chan N, Gonzalez R, Jang GH, Bronsert P, Fischer SE, Gallinger S, Grünwald BT, Khokha R.

J Pathol. 261(4), 2023

 

Differential DNA damage repair and PARP inhibitor vulnerability of the mammary epithelial lineages

Kim H, Aliar K, Tharmapalan P, McCloskey CW, Kuttanamkuzhi A, Grünwald BT, Palomero L, Mahendralingam MJ, Waas M, Mer AS, Elliott MJ, Zhang B, Al-Zahrani KN, Langille ER, Parsons M, Narala S, Hofer S, Waterhouse PD, Hakem R, Haibe-Kains B, Kislinger T, Schramek D, Cescon DW, Pujana MA, Berman HK, Khokha R.
 

Cell Rep. 42(10), 2023

 

2021

Spatially confined sub-tumor microenvironments in pancreatic cancer.

Grünwald BT, Devisme A, Andrieux G, Vyas F, Aliar K, McCloskey CW, Macklin A, Jang GH, Denroche R, Romero JM, Bavi P, Bronsert P, Notta F, O'Kane G, Wilson J, Knox J, Tamblyn L, Udaskin M, Radulovich N, Fischer SE, Boerries M, Gallinger S, Kislinger T, Khokha R.

Cell.184(22), 2021

 

TIMP1 expression underlies sex disparity in liver metastasis and survival in pancreatic cancer.

Hermann CD, Schoeps B, Eckfeld C, Munkhbaatar E, Kniep L, Prokopchuk O, Wirges N, Steiger K, Häußler D, Knolle P, Poulton E, Khokha R, Grünwald BT, Demir IE, Krüger A.

J Exp Med. 218(11), 2021

 

Abnormal B-cell development in TIMP-deficient bone marrow.

Weiss A, Saw S, Aiken A, Aliar K, Shao YW, Fang H, Narala S, Shetty R, Waterhouse PD, Khokha R.

Blood Adv. 5(20), 2021

 

 

Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development and tumorigenesis.

Li L, Guturi KKN, Gautreau B, Patel PS, Saad A, Morii M, Mateo F, Palomero L, Barbour H, Gomez A, Ng D, Kotlyar M, Pastrello C, Jackson HW, Khokha R, Jurisica I, Affar EB, Raught B, Sanchez O, Alaoui-Jamali M, Pujana MA, Hakem A, Hakem R.

J Clin Invest. 131(13), 2021

 

Mammary epithelial cells have lineage-rooted metabolic identities.

Mahendralingam MJ, Kim H, McCloskey CW, Aliar K, Casey AE, Tharmapalan P, Pellacani D, Ignatchenko V, Garcia-Valero M, Palomero L, Sinha A, Cruickshank J, Shetty R, Vellanki RN, Koritzinsky M, Stambolic V, Alam M, Schimmer AD, Berman HK, Eaves CJ, Pujana MA, Kislinger T, Khokha R.

Nat Metab. 3(5), 2021

 

2020

GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer.

O'Kane GM, Grünwald BT, Jang GH, Masoomian M, Picardo S, Grant RC, Denroche RE, Zhang A, Wang Y, Lam B, Krzyzanowski PM, Lungu IM, Bartlett JMS, Peralta M, Vyas F, Khokha R, Biagi J, Chadwick D, Ramotar S, Hutchinson S, Dodd A, Wilson JM, Notta F, Zogopoulos G, Gallinger S, Knox JJ, Fischer SE.

Clin Cancer Res. 26(18), 2020

 

A Four-Chemokine Signature Is Associated with a T-cell-Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer.

Romero JM, Grünwald B, Jang GH, Bavi PP, Jhaveri A, Masoomian M, Fischer SE, Zhang A, Denroche RE, Lungu IM, De Luca A, Bartlett JMS, Xu J, Li N, Dhaliwal S, Liang SB, Chadwick D, Vyas F, Bronsert P, Khokha R, McGaha TL, Notta F, Ohashi PS, Done SJ, O'Kane GM, Wilson JM, Knox JJ, Connor A, Wang Y, Zogopoulos G, Gallinger S.

Clin Cancer Res. 26(8), 2020

 

2019

 

 

Metalloproteases: On the Watch in the Hematopoietic Niche.

Saw S, Weiss A, Khokha R, Waterhouse PD.

Trends Immunol. 40(11), 2019

 

Saw S, Aiken A, Fang H, McKee TD, Bregant S, Sanchez O, Chen Y, Weiss A, Dickson BC, Czarny B, Sinha A, Fosang A, Dive V, Waterhouse PD, Kislinger T, Khokha R.

Metalloprotease inhibitor TIMP proteins control FGF-2 bioavailability and regulate skeletal growth.

J Cell Biology 218(9), 2019

 

Tharmapalan P, Mahendralingam M, Berman HK, Khokha R.

Mammary stem cells and progenitors: targeting the roots of breast cancer for prevention.

EMBO Journal 38:14, 2019

 

Shehata M, Kim H, Vellanki R, Waterhouse PD, Mahendralingam M, Casey AE, Koritzinsky M, Khokha R.

Identifying the murine mammary cell target of metformin exposure.

Communications Biology 2:192, 2019

 

Joshi PA, Waterhouse PD, Kasaian K, Fang H, Gulyaeva O, Sul HS, Boutros PC, Khokha R.

PDGFRα+ stromal adipocyte progenitors transition into epithelial cells during lobulo-alveologenesis in the murine mammary gland.

Nature Communications 10:1760, 2019

 

Chen Y, Aiken A, Saw S, Weiss A, Fang H, Khokha R.

TIMP Loss Activates Metalloproteinase-TNFα-DKK1 Axis To Compromise Wnt Signaling and Bone Mass.

J Bone Miner Res. 34:182-194, 2019

 

Shao YW, Wood GA, Lu J, Tang QL, Liu J, Molyneux S, Chen Y, Fang H, Adissu H, McKee T, Waterhouse P, Khokha R.

Cross-species genomics identifies DLG2 as a tumor suppressor in osteosarcoma.

Oncogene. 38:291-298, 2019

 

2018

Li L, Guturi KKN, Gautreau B, Patel PS, Saad A, Morii M, Mateo F, Palomero L, Barbour H, Gomez A, Ng D, Kotlyar M, Pastrello C, Jackson HW, Khokha R, Jurisica I, Affar EB, Raught B, Sanchez O, Alaoui-Jamali M, Pujana MA, Hakem A, Hakem R.

Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development and tumorigenesis.

J Clinical Investigation 128:4525-4542, 2018

 

Shehata M, Waterhouse PD, Casey AE, Fang H, Hazelwood L, Khokha R.

Proliferative heterogeneity of murine epithelial cells in the adult mammary gland.

Communications Biol 13:111, 2018

 

Casey AE, Sinha A, Singhania R, Livingstone J, Waterhouse P, Tharmapalan P, Cruickshank J, Shehata M, Drysdale E, Fang H, Kim H, Isserlin R, Bailey S, Medina T, Deblois G, Shiah YJ, Barsyte-Lovejoy D, Hofer S, Bader G, Lupien M, Arrowsmith C, Knapp S, De Carvalho D, Berman H, Boutros PC, Kislinger T, Khokha R.

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

J Cell Biology 217:2951-2974, 2018

 

Tang Q, Lu J, Zou C, Shao Y, Chen Y, Narala S, Fang H, Xu H, Wang J, Shen J, Khokha R.

CDH4 is a novel determinant of osteosarcoma tumorigenesis and metastasis.

Oncogene, 37:3617-3630, 2018

 

Selected Lifetime Publications

Jackson HW, Waterhouse P, Defamie V, Khokha R

TIMPs: versatile regulators in cancer.

Nature Rev Cancer 17:38-53, 2016; Journal cover

 

Chen Y, Di Grappa MA, Molyneux S, McKee TD, Waterhouse P, Penninger JM, Khokha R  

RANKL blockade prevents and treats aggressive osteosarcomas.

Science Translation Medicine 7:317ra197, 2015; Received editorial highlight and in news

 

Moriarity BS, Otto GM, Rahrmann EP, Rathe SK, Wold NK … Khokha R … Largaespada DA

A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma…

Nature Genetics 47:615-624, 2015; In news; F1000

 

Joshi PA, Goodwin PJ, Khokha R

Progesterone Exposure and Breast Cancer Risk: Understanding the Biological Roots.

JAMA Oncology 1:283-285; 2015

 

Jackson HW, Waterhouse P, Sinha A, Kislinger T, Berman HK, Khokha R

Expansion of stem cells counteracts age-related mammary regression in Timp1/Timp3 null mice.

Nature Cell Biology 17:217-227, 2015; Featured in News & Views; UHN, CCS & U of T highlights

 

Joshi PA, Waterhouse PD, Kannan N, Narala S, Fang H, Di Grappa MA … Eaves C, Khokha R

Rank Signaling Amplifies Wnt-Responsive Mammary Progenitors through R-Spondin1.

Stem Cell Reports 5:31-44, 2015

 

Defamie V, Sanchez O, Murthy A, Khokha R

TIMP3 controls cell fate to confer hepatocellular carcinoma resistance.

Oncogene 34:4098-4108, 2015   

 

Beristain AG, Molyneux SD, Joshi PA… Kirschner LS, Privé GG, Pujana MA, Khokha R

PKA signaling drives mammary tumorigenesis through Src.

Oncogene 34:1160-1173, 2015

 

Shiah Y-J, Tharmapalan, Casey AE, Joshi PA, McKee TD, Jackson HW, Beristain, AG … Khokha R

A progesterone-CXCR4 axis controls mammary progenitor cell fate in the adult gland.

Stem Cell Reports 4:312-322, 2015

 

Molyneux SD, Waterhouse PD, Shelton D… Wunder JS, Izsvák Z, Lupien M, Mak TW, Khokha R

Human somatic cell mutagenesis creates genetically tractable sarcomas.

Nature Genetics 46:964-972, 2014; Featured in News & Views

 

Shimoda M, Principe S, Jackson H ...Okada Y, Ailles L Ludwig A, Wrana JL, Kislinger T, Khokha R

Loss of the Timp gene family is sufficient for acquisition of the CAF-like cell state.

Nature Cell Biology 16:889-901, 2014; Received commentary

 

Alexander CM, Joshi PA, Khokha R

Fully interlocking: a story of teamwork among breast epithelial cells.

Developmental Cell 28:114-115, 2014

 

Khokha R, Murthy A, Weiss A

Metalloproteinases and their natural inhibitors in inflammation and immunity.

Nature Rev Immunology 13:649-665, 2013

 

Murthy A, Shao YW, Narala SR, Molyneux SD, Zúñiga-Pflücker JC, Khokha R

Notch activation by the metalloproteinase ADAM17 regulates myeloproliferation and atopic barriers

Immunity 36:105-119, 2012

 

McIlwain DR, Lang PA, Maretzky T…Khokha R, Ohashi P, Blobel CP, Mak TW

iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS.

Science 335:229-232, 2012

 

Joshi PA, Jackson HW, Beristain AG, Di Grappa MA, Mote PA, Clarke CL … Waterhouse PD, Khokha R

Progesterone induces adult mammary stem cell expansion.

Nature 465:803-807, 2010; Featured in News & Views, Nat Rev Cancer, In news, F1000

 

Schramek D, Leibbrandt A … Khokha R, Ormandy CJ, Widschwendter M, Schett G, Penninger JM

Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer.

Nature 2010 468:98-102, 2010

 

Molyneux SD, Di Grappa MA, Beristain AG, McKee TD, Wai DH, Paderova J, Kashyap M … Khokha R

Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice.

J Clinical Investigation 120:3310-3325, 2010

 

Murthy A, Defamie V, Smookler DS, Di Grappa MA, Horiuchi K, Federici M, Sibilia M, Blobel CP, Khokha R

Ectodomain shedding of EGFR ligands & TNFR1 dictates hepatocyte apoptosis during fulminant hepatitis ...

J Clinical Investigation 120:2731-2744, 2010; Received editorial highlight

 

Jones DH, Nakashima T, Sanchez OH … Khokha R, Wada T, Penninger JM

Regulation of cancer cell migration and bone metastasis by RANKL.

Nature 440:692-696, 2006

 

Fedak PW, Smookler DS, Kassiri Z, Ohno N, Leco KJ, Cruz, W, Weisel RD, Li R-K, Khokha R

Timp-3 deficiency leads to dilated cardiomyopathy.

Circulation 110:2401-2409, 2004

Mohammed FF, Smookler DS, Taylor SE, Fingleton B, Kassiri Z, Sanchez OH…Khokha R

Abnormal TNF activity in Timp3-/- mice leads to hepatic inflammation & liver regeneration failure.

Nature Genetics 36:969-977, 2004; Featured in News & Views; F1000

 

Fata JE, Leco KJ, Voura EB, Yu HY, Waterhouse P, Murphy G, Moorehead RA, Khokha R    

Accelerated apoptosis in Timp-3-deficient mammary gland.

J Clinical Investigation 108:831-841, 2001

 

Leco KJ, Waterhouse P, Sanchez OH, Gowing KL, Poole AR, Wakeham A, Mak TW, Khokha R

Spontaneous air space enlargement in lungs of mice lacking TIMP-3.

J Clinical Investigation 108:817-829, 2001; Commentary & Journal cover

 

Fata JE, Chaudhary V, Khokha R

Cellular turnover in the mammary tissue is correlated with the systemic levels of progesterone and not…

Biology of Reproduction 10:243-248, 2001

 

Fata JE, Kong YY, Li J, Sasaki T, Irie-Sasaki J, Moorehead RA, Elliott R…Khokha R, Penninger JM

The OPGL is essential for mammary gland development.

Cell 103:41-50, 2000

 

Granovsky M, Fata J, Pawling J, Muller WJ, Khokha R, Dennis JW

Suppression of tumor growth and metastasis in Mgat5-deficient mice.

Nature Medicine 6:306-312, 2000

 

Martin DC, Fowlkes JL, Babic B, Khokha R

IGF I signaling in neoplastic proliferation is blocked by transgenic TIMP-1.

J Cell Biology 146:881-892, 1999

 

Khokha R

Suppression of tumorigenic and metastatic abilities of B16-F10 melanoma cells in vivo by Timp-1 overexpression.   

J National Cancer Institute 86:299-304, 1994          

 

Khokha R, Waterhouse P, Yagel S, Lala PK, Overall CM, Norton G, Denhardt DT

Antisense RNA-induced reduction in TIMP levels confers oncogenicity on Swiss 3T3 cells.

Science 243:947-950, 1989