Daniel Johnson, PhD

Professor in Residence
Primary Thematic Area
Cancer Biology & Cell Signaling
M_Oto-General OHNS
Secondary Thematic Area
Human Genetics
Research Summary
We investigate molecular mechanisms that contribute to the development and progression of head and neck cancer, and seek to develop novel therapeutic agents for this disease
[email protected]

Work in our lab employs multiple model systems to investigate the biology and therapy of head and neck squamous cell carcinoma (HNSCC), including isogenic cell lines, organoids, patient-derived xenograft tumors, genetically engineered mice, and primary patient specimens.  

Our research is focused on understanding the molecular mechanisms that contribute to the origin and progression of HNSCC, and the development of novel therapeutic agents and strategies for this disease. We are particularly interested in combating the intrinsic and acquired resistance to anti-cancer agents that characterizes the majority of HNSCC patient tumors. Work from our lab has shown that overexpression of anti-apoptotic Bcl-2 family members and/or hyperactivation of STAT3 transcription factor contribute to HNSCC drug resistance. We have employed small molecule inhibitors of Bcl-2/Bcl-XL/Mcl-1, as well as proteasome inhibitors, to develop synergistic co-targeting strategies to overcome resistance arising for overexpression of Bcl-2 family members. To combat the effects of STAT3 hyperactivation, we co-invented an highly novel decoy oligonucleotide inhibitor for this previously undruggable oncogene. Current efforts are focused on moving the STAT3 decoy to clinical evaluation in patients with HNSCC. Additional studies in our lab have shown that mutations in caspase-8 protease, which occur frequently in HNSCC tumors, contribute to disease progression by abrogating cell death mediated by death ligands such as TRAIL and TNF. Ongoing studies are aimed at developing further in vivo and organoid models of HNSCC for investigation of drug resistance mechanisms and evaluation of novel precision medicine therapeutic strategies.

Current laboratory goals include:

  1. To determine the impact of STAT3 inhibition on HNSCC tumors and immune components in the tumor microenvironment.
  2. To determine the mechanistic impact of caspase-8 mutations in HNSCC.
  3. To determine the molecular mechanisms underlying the unique vulnerability of Fanconi Anemia patients to development of HNSCC.

Publications

PIK3CA mutations in colorectal and breast cancer: impact on oncogenesis and response to nonsteroidal anti-inflammatory drugs. In: Targeting Cell Survival Pathways to Enhance Response to Chemotherapy. Chapter 6, pgs. 123-144. Editor: DE Johnson. Els

PIK3CA mutations in colorectal and breast cancer: impact on oncogenesis and response to nonsteroidal anti-inflammatory drugs. In: Targeting Cell Survival Pathways to Enhance Response to Chemotherapy. Chapter 6, pgs. 123-144. Editor: DE Johnson. Els

Zhu RT, Gutkind JS, Johnson DE, Grandis JR

Targeting members of the epidermal growth factor receptor family to improve response to chemotherapy. In: Targeting Cell Survival Pathways to Enhance Response to Chemotherapy. Chapter 1, pgs. 1-23. Editor: DE Johnson. Elsevier. ISBN: 978-0-12-8164

Targeting members of the epidermal growth factor receptor family to improve response to chemotherapy. In: Targeting Cell Survival Pathways to Enhance Response to Chemotherapy. Chapter 1, pgs. 1-23. Editor: DE Johnson. Elsevier. ISBN: 978-0-12-8164

O’Keefe RA, Grandis JR, Johnson DE

Guidelines for the use and interpretation of assays for monitoring autophagy.

Autophagy

Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, Ahn HJ, Ait-Mohamed O, Ait-Si-Ali S, Akematsu T, Akira S, Al-Younes HM, Al-Zeer MA, Albert ML, Albin RL, Alegre-Abarrategui J, Aleo MF, Alirezaei M, Almasan A, Almonte-Becerril M, Amano A, Amaravadi R, Amarnath S, Amer AO, Andrieu-Abadie N, Anantharam V, Ann DK, Anoopkumar-Dukie S, Aoki H, Apostolova N, Arancia G, Aris JP, Asanuma K, Asare NY, Ashida H, Askanas V, Askew DS, Auberger P, Baba M, Backues SK, Baehrecke EH, Bahr BA, Bai XY, Bailly Y, Baiocchi R, Baldini G, Balduini W, Ballabio A, Bamber BA, Bampton ET, Bánhegyi G, Bartholomew CR, Bassham DC, Bast RC, Batoko H, Bay BH, Beau I, Béchet DM, Begley TJ, Behl C, Behrends C, Bekri S, Bellaire B, Bendall LJ, Benetti L, Berliocchi L, Bernardi H, Bernassola F, Besteiro S, Bhatia-Kissova I, Bi X, Biard-Piechaczyk M, Blum JS, Boise LH, Bonaldo P, Boone DL, Bornhauser BC, Bortoluci KR, Bossis I, Bost F, Bourquin JP, Boya P, Boyer-Guittaut M, Bozhkov PV, Brady NR, Brancolini C, Brech A, Brenman JE, Brennand A, Bresnick EH, Brest P, Bridges D, Bristol ML, Brookes PS, Brown EJ, Brumell JH, Brunetti-Pierri N, Brunk UT, Bulman DE, Bultman SJ, Bultynck G, Burbulla LF, Bursch W, Butchar JP, Buzgariu W, Bydlowski SP, Cadwell K, Cahová M, Cai D, Cai J, Cai Q, Calabretta B, Calvo-Garrido J, Camougrand N, Campanella M, Campos-Salinas J, Candi E, Cao L, Caplan AB, Carding SR, Cardoso SM, Carew JS, Carlin CR, Carmignac V, Carneiro LA, Carra S, Caruso RA, Casari G, Casas C, Castino R, Cebollero E, Cecconi F, Celli J, Chaachouay H, Chae HJ, Chai CY, Chan DC, Chan EY, Chang RC, Che CM, Chen CC, Chen GC, Chen GQ, Chen M, Chen Q, Chen SS, Chen W, Chen X, Chen X, Chen X, Chen YG, Chen Y, Chen Y, Chen YJ, Chen Z, Cheng A, Cheng CH, Cheng Y, Cheong H, Cheong JH, Cherry S, Chess-Williams R, Cheung ZH, Chevet E, Chiang HL, Chiarelli R, Chiba T, Chin LS, Chiou SH, Chisari FV, Cho CH, Cho DH, Choi AM, Choi D, Choi KS, Choi ME, Chouaib S, Choubey D, Choubey V, Chu CT, Chuang TH, Chueh SH, Chun T, Chwae YJ, Chye ML, Ciarcia R, Ciriolo MR, Clague MJ, Clark RS, Clarke PG, Clarke R, Codogno P, Coller HA, Colombo MI, Comincini S, Condello M, Condorelli F, Cookson MR, Coombs GH, Coppens I, Corbalan R, Cossart P, Costelli P, Costes S, Coto-Montes A, Couve E, Coxon FP, Cregg JM, Crespo JL, Cronjé MJ, Cuervo AM, Cullen JJ, Czaja MJ, D'Amelio M, Darfeuille-Michaud A, Davids LM, Davies FE, De Felici M, de Groot JF, de Haan CA, De Martino L, De Milito A, De Tata V, Debnath J, Degterev A, Dehay B, Delbridge LM, Demarchi F, Deng YZ, Dengjel J, Dent P, Denton D, Deretic V, Desai SD, Devenish RJ, Di Gioacchino M, Di Paolo G, Di Pietro C, Díaz-Araya G, Díaz-Laviada I, Diaz-Meco MT, Diaz-Nido J, Dikic I, Dinesh-Kumar SP, Ding WX, Distelhorst CW, Diwan A, Djavaheri-Mergny M, Dokudovskaya S, Dong Z, Dorsey FC, Dosenko V, Dowling JJ, Doxsey S, Dreux M, Drew ME, Duan Q, Duchosal MA, Duff K, Dugail I, Durbeej M, Duszenko M, Edelstein CL, Edinger AL, Egea G, Eichinger L, Eissa NT, Ekmekcioglu S, El-Deiry WS, Elazar Z, Elgendy M, Ellerby LM, Eng KE, Engelbrecht AM, Engelender S, Erenpreisa J, Escalante R, Esclatine A, Eskelinen EL, Espert L, Espina V, Fan H, Fan J, Fan QW, Fan Z, Fang S, Fang Y, Fanto M, Fanzani A, Farkas T, Farré JC, Faure M, Fechheimer M, Feng CG, Feng J, Feng Q, Feng Y, Fésüs L, Feuer R, Figueiredo-Pereira ME, Fimia GM, Fingar DC, Finkbeiner S, Finkel T, Finley KD, Fiorito F, Fisher EA, Fisher PB, Flajolet M, Florez-McClure ML, Florio S, Fon EA, Fornai F, Fortunato F, Fotedar R, Fowler DH, Fox HS, Franco R, Frankel LB, Fransen M, Fuentes JM, Fueyo J, Fujii J, Fujisaki K, Fujita E, Fukuda M, Furukawa RH, Gaestel M, Gailly P, Gajewska M, Galliot B, Galy V, Ganesh S, Ganetzky B, Ganley IG, Gao FB, Gao GF, Gao J, Garcia L, Garcia-Manero G, Garcia-Marcos M, Garmyn M, Gartel AL, Gatti E, Gautel M, Gawriluk TR, Gegg ME, Geng J, Germain M, Gestwicki JE, Gewirtz DA, Ghavami S, et al

Lack of toxicity of a STAT3 decoy oligonucleotide.

Cancer chemotherapy and pharmacology

Sen M, Tosca PJ, Zwayer C, Ryan MJ, Johnson JD, Knostman KA, Giclas PC, Peggins JO, Tomaszewski JE, McMurray TP, Li C, Leibowitz MS, Ferris RL, Gooding WE, Thomas SM, Johnson DE, Grandis JR

The intrinsic (mitochondrial) death pathway and new cancer therapeutics: Bcl-2 family in focus. In: Apoptotic Pathways as Targets for Novel Therapies in Cancer and Other Diseases. Editors: M Los and SB Gibson. Kluwer Academic Press. ISBN: 0-387-2

The intrinsic (mitochondrial) death pathway and new cancer therapeutics: Bcl-2 family in focus. In: Apoptotic Pathways as Targets for Novel Therapies in Cancer and Other Diseases. Editors: M Los and SB Gibson. Kluwer Academic Press. ISBN: 0-387-2

Shangary S, Oliver CL, Johnson DE